miR-224、miR-146b、miR-215和miR-135a 对脂肪细胞分化和脂质代谢的作用研究
|
摘要
近年来,大量的研究表明miRNA在脂肪细胞分化和脂质代谢方面起着重要的调控作用,miRNA通过靶向脂肪生成的重要转录因子和脂质代谢关键基因调控脂肪细胞分化和脂质代谢。本论文基于5月龄大白猪和梅山猪的背部脂肪组织Solexa测序获得的差异表达的miRNAs,通过对miRNAs的序列分析、靶基因预测和功能分析等,靶定miR-224、miR-146b、miR-215和miR-135a。采用双荧素酶报告基因检测、Q-PCR、Western blotting等方法对4个miRNAs的作用和功能进行了研究,主要研究结果如下：1. miR-224调控脂肪细胞分化和脂肪酸代谢
经UCSC网站比对发现,包括猪在内的多种哺乳动物的miR-224定位在X染色体上的相同的位置,即GABRE基因的内含子处；通过对miR-224的前体序列和成熟序列进行比对,它们在哺乳动物中的序列高度保守。
通过多种靶基因预测软件预测发现,EGR2和ACSL4可能是miR-224的靶基因。双荧光素酶报告试验证实,与对照组相比, miR-224-5p明显抑制了EGR2-3'UTR和ACSL4-3'UTR双荧光素酶报告载体的荧光活性。
在3T3-L1前脂肪细胞分化过程中miR-224-5p表达量先下降后上升。miR-224-5p转染组经诱导分化甘油三脂含量明显低于对照组,同时脂肪细胞分化标志基因PPARγ、aP2的表达量也明显下降。
miR-224-5p在3T3-L1前脂肪细胞分化早期通过直接靶向EGR2,抑制其表达,进而抑制其下游的C/EBPβ基因的表达；抑制表达的EGR2基因至少是部分通过抑制C/EBPβ的表达抑制脂肪细胞分化标志基因PPARy, aP2的表达,导致甘油三脂积累受阻,从而抑制脂肪细胞分化。
在脂肪分化晚期,miR-224-5p直接靶向ACSL4,抑制ACSL4的mRNA和蛋白质的表达,从而抑制脂肪酸p氧化过程中脂肪酸的活化,致使脂肪酸p氧化过程受阻,从而调控脂肪酸代谢。
本研究首次证实了miR-224通过靶向EGR2和ACSL4在脂肪生成的不同时期发挥着不同的生物学功能。
2. miR-146b调控脂肪细胞分化
miR-146b序列比对发现,miR-146b的成熟序列有很高的保守性。通过多种靶基因预测软件预测发现,Runx1t1和Smad4可能是miR.146b的靶基因。双荧光素酶报告试验证实,与对照组相比,miR-146-5p明显抑制了Runx1t1-3'UTR和Smad4-3'UTR双荧光素酶报告载体的荧光活性。
miR-146b-5p转染组经诱导分化后甘油三脂含量明显高于对照组,同时脂肪细胞分化标志基因C/EBPα、PPARγ、αP2的mRNA和蛋白表达量也明显上升。
miR-146b-5p在3T3-L1前脂肪细胞分化早期靶向Runx1t1,抑制其表达,可能通过影响Runx1t1与C、EBPβ的相互作用从而调控C/EBPα启动子的活性促进脂肪细胞的分化；miR-146b-5p还能够靶向Smad4,抑制其表达,至少是部分通过抑制TGFβ通路下游基因CTGF的表达促进脂肪细胞的分化。
3.miR-215调控脂肪细胞分化
miR-215序列比对发现,miR-215的成熟序列有很高的保守性。通过多种靶基因预测软件预测发现,FNDC3B和CTNNBIP1可能是miR-215的靶基因。双荧光素酶报告试验证实,与对照组相比,miR-215-5p明显抑制了FNDC3B一3'UTR和CTNNBIP1-3'UTR双荧光素酶报告载体的荧光活性。
miR-215-5p转染组经诱导分化甘油三脂含量明显低于对照组,同时脂肪细胞分化标志基因C/EBPα、PPARγ、αP2的mRNA和蛋白表达量也明显降低。
miR-215-5p在3T3-Ll前脂肪细胞分化早期靶向FNDC3B,抑制其表达,从而抑制脂肪细胞的分化；miR-215-5p还能够靶向CTNNBIPl,抑制其表达,通过促进Wnt通路下游基因c-myc和CCNDl的表达抑制脂肪的分化。
4. miR-135a调控脂肪酸碳链的延长
miR-135a序列比对发现,miR-135a的成熟序列有很高的保守性。通过多种靶基因预测软件预测发现,ELOVL2和ElOVL6可能是miR-135a的靶基因。双荧光素酶报告试验证实,与对照组相比,miR-135a-5p明显抑制了ELOVL2和ELOVL6双荧光素酶报告载体的荧光活性。
Q-PCR检测显示：在小鼠3T3-L1脂肪细胞中,miR-135a-5p抑制了ELOVL6的表达；而在小鼠Hepa1-6肝脏细胞中,ELOVL2和ELoVL6的表达都被miR-135a-5p的超表达所抑制。mir-135a可能参与调控脂肪酸碳链的延长。
综上所述,本研究的结论是：①miR-224在脂肪细胞分化早期通过靶向EGR2抑制脂肪细胞的分化,在脂肪细胞分化晚期通过靶向ACSL4调控脂肪酸代谢；②miR-146b在脂肪细胞分化早期通过靶向Runx1t1和Smad4促进脂肪细胞分化；③miR-215在脂肪细胞分化早期通过靶向FNDC3B和CTNNBIP1抑制脂肪细胞分化；④miR-135a可能参与调控脂肪酸碳链的延长。
In recent years, more and more studies indicate that miRNA plays an important role in adipocyte differentiation and lipid metabolism by targeting the key adipogenic transcription factors and the key genes of lipid metabolism. This study aimed to investigate the effect of miRNA on adipocyte differentiation and lipid metabolism based on the differentional expressions miRNAs of the backfat tissues of150-day-old Large White and Meishan pigs by Solexa sequencing. Then, these miRNAs with differentional expressions were subjected to sequence analysis, target prediction and function analysis and miR-224, miR-146b, miR-215and miR-135a became the object of our study. The four miRNAs were studied by using the dual luciferase reporter gene analysis, Q-PCR assay and Western blotting etc. The main results as follows:1. mR-224regulates adipocyte differentiation and fatty acid metabolism
Ssc-miR-224is located on Chromosome X and the same miRNA of the other mammals is also present in the same location, the intron of GABRE, using UCSC website. Furthermore, the pre-miRNAs and the mature miRNAs of miR-224are highly conserved in many mammals.
Several bioinformatics target prediction softwares were used to predict targets of miR-224. The results showed that EGR2and ACSL4may be the targets of miR-224. miR-224-5p significantly inhibited the luciferase activity of EGR2and ACSL43'UTR plasmid when compared to control groups through the dual luciferase reporter gene analysis.
miR-224-5p abundance decreases first and then increases during adipogenesis of3T3-L1cells. The content of triglyceride was lower in miR-224-5p group, and meanwhile the expression levels of adipogenic maker genes (PPARy, aP2) were also decreased.The mRNA expression levels of EGR2was suppressed by miR-224-5p during early adipogenesis and the downstream gene C/EBPβ was also suppressed. miR-224-5p could suppress EGR2expression by directly targeting it at least in part through indirect suppression of the C/EBPβ expression, decreasing the expressions of PPARy, aP2and accumulation of triglyceride, resulting in the inhibition of adipocyte differentiation. The mRNA and protein expression levels of ACSL4were both suppressed by miR-224-5p at terminal differentiation, inhibiting fatty acid activation of fatty acid β-oxidation and fatty acid β-oxidation, regulating fatty acid metabolism.
We first found that miR-224plays different roles on different stages of adipogenesis by directly targeting EGR2and ACSL4.
2. miR-146b regulates adipocyte differentiation
The mature miRNAs of miR-146b are highly conserved in many mammals through sequence alignment.Several bioinformatics target prediction softwares were used to predict targets of miR-146b. The results showed that Runxltl and Smad4may be the targets of miR-146b. miR-146b-5p significantly inhibited the luciferase activity of Runxltl and Smad43'UTR plasmid when compared to control groups through the dual luciferase reporter gene analysis.
The content of triglyceride was higher in miR-146b-5p group, and meanwhile the mRNA and protein expression levels of adipogenic maker genes(C/EBPa, PPARy, aP2) were also upregulated.
miR-146b could suppress Runxltl expression by directly targeting it and may control the interaction of Runxltl and C/EBPβ, then prevent the transcriptional activation of the C/EBPa promoter and promote adipocyte differentiation. Furthermore, miR-146b could suppress Smad4expression by directly targeting it at least in part through suppression of the CTGF expression which is the downstream gene of TGFβ signaling pathway, resulting in promotion of adipocyte differentiation.
3. miR-215regulates adipocyte differentiation
The mature miRNAs of miR-215are highly conserved in many mammals through sequence alignment. Several bioinformatics target prediction softwares were used to predict targets of miR-215. The results showed that FNDC3B and CTNNBIP1may be the targets of miR-215. miR-215-5p significantly inhibited the luciferase activity of FNDC3B and CTNNBIP13'UTR plasmid when compared to control groups through the dual luciferase reporter gene analysis.
The content of triglyceride was lower in miR-215-5p group, and meanwhile the mRNA and protein expression levels of adipogenic maker genes(C/EBPa, PPARy, aP2) were also decreased.
miR-215-5p could suppress FNDC3B expression by directly targeting it and impair adipocyte differentiation. Furthermore, miR-215-5p could suppress CTNNBIP1expression by directly targeting it through promotion of the c-myc and CCND1expression which is the downstream gene of Wnt/β-catenin signaling pathway, resulting in inhibition of adipocyte differentiation.
4. miR-135a regulates fatty acid elongation
The mature miRNAs of miR-135a are highly conserved in many mammals through sequence alignment. Several bioinformatics target prediction softwares were used to predict targets of miR-135a. The results showed that ELOVL2and ELOVL6may be the targets of miR-135a. miR-135a-5p significantly inhibited the luciferase activity of ELOVL2and ELOVL63'UTR plasmid when compared to control groups through the dual luciferase reporter gene analysis.
miR-215-5p could suppress ELOVL6expression in mouse3T3-L1adipocytes and miR-215-5p also could suppress ELOVL2and ELOVL6in mouse Hepa1-6hepatocytes by using Q-PCR. miR-135a may regulate fatty acid elongation.
In summary, the conclusions of this study are:①miR-224could suppress EGR2expression by directly targeting it and impair adipocyte differentiation during early adipogenesis; miR-224also could suppress ACSL4expression by directly targeting it and regulate fatty acid metabolism.②miR-146b could suppress Runxltl and Smad4expression by directly targeting them and promote adipocyte differentiation during early adipogenesis.③miR-215could suppress FNDC3B and CTNNBIP1expression by directly targeting them and impair adipocyte differentiation during early adipogenesis.④miR-135a may regulate fatty acid elongation.
经UCSC网站比对发现,包括猪在内的多种哺乳动物的miR-224定位在X染色体上的相同的位置,即GABRE基因的内含子处；通过对miR-224的前体序列和成熟序列进行比对,它们在哺乳动物中的序列高度保守。
通过多种靶基因预测软件预测发现,EGR2和ACSL4可能是miR-224的靶基因。双荧光素酶报告试验证实,与对照组相比, miR-224-5p明显抑制了EGR2-3'UTR和ACSL4-3'UTR双荧光素酶报告载体的荧光活性。
在3T3-L1前脂肪细胞分化过程中miR-224-5p表达量先下降后上升。miR-224-5p转染组经诱导分化甘油三脂含量明显低于对照组,同时脂肪细胞分化标志基因PPARγ、aP2的表达量也明显下降。
miR-224-5p在3T3-L1前脂肪细胞分化早期通过直接靶向EGR2,抑制其表达,进而抑制其下游的C/EBPβ基因的表达；抑制表达的EGR2基因至少是部分通过抑制C/EBPβ的表达抑制脂肪细胞分化标志基因PPARy, aP2的表达,导致甘油三脂积累受阻,从而抑制脂肪细胞分化。
在脂肪分化晚期,miR-224-5p直接靶向ACSL4,抑制ACSL4的mRNA和蛋白质的表达,从而抑制脂肪酸p氧化过程中脂肪酸的活化,致使脂肪酸p氧化过程受阻,从而调控脂肪酸代谢。
本研究首次证实了miR-224通过靶向EGR2和ACSL4在脂肪生成的不同时期发挥着不同的生物学功能。
2. miR-146b调控脂肪细胞分化
miR-146b序列比对发现,miR-146b的成熟序列有很高的保守性。通过多种靶基因预测软件预测发现,Runx1t1和Smad4可能是miR.146b的靶基因。双荧光素酶报告试验证实,与对照组相比,miR-146-5p明显抑制了Runx1t1-3'UTR和Smad4-3'UTR双荧光素酶报告载体的荧光活性。
miR-146b-5p转染组经诱导分化后甘油三脂含量明显高于对照组,同时脂肪细胞分化标志基因C/EBPα、PPARγ、αP2的mRNA和蛋白表达量也明显上升。
miR-146b-5p在3T3-L1前脂肪细胞分化早期靶向Runx1t1,抑制其表达,可能通过影响Runx1t1与C、EBPβ的相互作用从而调控C/EBPα启动子的活性促进脂肪细胞的分化；miR-146b-5p还能够靶向Smad4,抑制其表达,至少是部分通过抑制TGFβ通路下游基因CTGF的表达促进脂肪细胞的分化。
3.miR-215调控脂肪细胞分化
miR-215序列比对发现,miR-215的成熟序列有很高的保守性。通过多种靶基因预测软件预测发现,FNDC3B和CTNNBIP1可能是miR-215的靶基因。双荧光素酶报告试验证实,与对照组相比,miR-215-5p明显抑制了FNDC3B一3'UTR和CTNNBIP1-3'UTR双荧光素酶报告载体的荧光活性。
miR-215-5p转染组经诱导分化甘油三脂含量明显低于对照组,同时脂肪细胞分化标志基因C/EBPα、PPARγ、αP2的mRNA和蛋白表达量也明显降低。
miR-215-5p在3T3-Ll前脂肪细胞分化早期靶向FNDC3B,抑制其表达,从而抑制脂肪细胞的分化；miR-215-5p还能够靶向CTNNBIPl,抑制其表达,通过促进Wnt通路下游基因c-myc和CCNDl的表达抑制脂肪的分化。
4. miR-135a调控脂肪酸碳链的延长
miR-135a序列比对发现,miR-135a的成熟序列有很高的保守性。通过多种靶基因预测软件预测发现,ELOVL2和ElOVL6可能是miR-135a的靶基因。双荧光素酶报告试验证实,与对照组相比,miR-135a-5p明显抑制了ELOVL2和ELOVL6双荧光素酶报告载体的荧光活性。
Q-PCR检测显示：在小鼠3T3-L1脂肪细胞中,miR-135a-5p抑制了ELOVL6的表达；而在小鼠Hepa1-6肝脏细胞中,ELOVL2和ELoVL6的表达都被miR-135a-5p的超表达所抑制。mir-135a可能参与调控脂肪酸碳链的延长。
综上所述,本研究的结论是：①miR-224在脂肪细胞分化早期通过靶向EGR2抑制脂肪细胞的分化,在脂肪细胞分化晚期通过靶向ACSL4调控脂肪酸代谢；②miR-146b在脂肪细胞分化早期通过靶向Runx1t1和Smad4促进脂肪细胞分化；③miR-215在脂肪细胞分化早期通过靶向FNDC3B和CTNNBIP1抑制脂肪细胞分化；④miR-135a可能参与调控脂肪酸碳链的延长。
In recent years, more and more studies indicate that miRNA plays an important role in adipocyte differentiation and lipid metabolism by targeting the key adipogenic transcription factors and the key genes of lipid metabolism. This study aimed to investigate the effect of miRNA on adipocyte differentiation and lipid metabolism based on the differentional expressions miRNAs of the backfat tissues of150-day-old Large White and Meishan pigs by Solexa sequencing. Then, these miRNAs with differentional expressions were subjected to sequence analysis, target prediction and function analysis and miR-224, miR-146b, miR-215and miR-135a became the object of our study. The four miRNAs were studied by using the dual luciferase reporter gene analysis, Q-PCR assay and Western blotting etc. The main results as follows:1. mR-224regulates adipocyte differentiation and fatty acid metabolism
Ssc-miR-224is located on Chromosome X and the same miRNA of the other mammals is also present in the same location, the intron of GABRE, using UCSC website. Furthermore, the pre-miRNAs and the mature miRNAs of miR-224are highly conserved in many mammals.
Several bioinformatics target prediction softwares were used to predict targets of miR-224. The results showed that EGR2and ACSL4may be the targets of miR-224. miR-224-5p significantly inhibited the luciferase activity of EGR2and ACSL43'UTR plasmid when compared to control groups through the dual luciferase reporter gene analysis.
miR-224-5p abundance decreases first and then increases during adipogenesis of3T3-L1cells. The content of triglyceride was lower in miR-224-5p group, and meanwhile the expression levels of adipogenic maker genes (PPARy, aP2) were also decreased.The mRNA expression levels of EGR2was suppressed by miR-224-5p during early adipogenesis and the downstream gene C/EBPβ was also suppressed. miR-224-5p could suppress EGR2expression by directly targeting it at least in part through indirect suppression of the C/EBPβ expression, decreasing the expressions of PPARy, aP2and accumulation of triglyceride, resulting in the inhibition of adipocyte differentiation. The mRNA and protein expression levels of ACSL4were both suppressed by miR-224-5p at terminal differentiation, inhibiting fatty acid activation of fatty acid β-oxidation and fatty acid β-oxidation, regulating fatty acid metabolism.
We first found that miR-224plays different roles on different stages of adipogenesis by directly targeting EGR2and ACSL4.
2. miR-146b regulates adipocyte differentiation
The mature miRNAs of miR-146b are highly conserved in many mammals through sequence alignment.Several bioinformatics target prediction softwares were used to predict targets of miR-146b. The results showed that Runxltl and Smad4may be the targets of miR-146b. miR-146b-5p significantly inhibited the luciferase activity of Runxltl and Smad43'UTR plasmid when compared to control groups through the dual luciferase reporter gene analysis.
The content of triglyceride was higher in miR-146b-5p group, and meanwhile the mRNA and protein expression levels of adipogenic maker genes(C/EBPa, PPARy, aP2) were also upregulated.
miR-146b could suppress Runxltl expression by directly targeting it and may control the interaction of Runxltl and C/EBPβ, then prevent the transcriptional activation of the C/EBPa promoter and promote adipocyte differentiation. Furthermore, miR-146b could suppress Smad4expression by directly targeting it at least in part through suppression of the CTGF expression which is the downstream gene of TGFβ signaling pathway, resulting in promotion of adipocyte differentiation.
3. miR-215regulates adipocyte differentiation
The mature miRNAs of miR-215are highly conserved in many mammals through sequence alignment. Several bioinformatics target prediction softwares were used to predict targets of miR-215. The results showed that FNDC3B and CTNNBIP1may be the targets of miR-215. miR-215-5p significantly inhibited the luciferase activity of FNDC3B and CTNNBIP13'UTR plasmid when compared to control groups through the dual luciferase reporter gene analysis.
The content of triglyceride was lower in miR-215-5p group, and meanwhile the mRNA and protein expression levels of adipogenic maker genes(C/EBPa, PPARy, aP2) were also decreased.
miR-215-5p could suppress FNDC3B expression by directly targeting it and impair adipocyte differentiation. Furthermore, miR-215-5p could suppress CTNNBIP1expression by directly targeting it through promotion of the c-myc and CCND1expression which is the downstream gene of Wnt/β-catenin signaling pathway, resulting in inhibition of adipocyte differentiation.
4. miR-135a regulates fatty acid elongation
The mature miRNAs of miR-135a are highly conserved in many mammals through sequence alignment. Several bioinformatics target prediction softwares were used to predict targets of miR-135a. The results showed that ELOVL2and ELOVL6may be the targets of miR-135a. miR-135a-5p significantly inhibited the luciferase activity of ELOVL2and ELOVL63'UTR plasmid when compared to control groups through the dual luciferase reporter gene analysis.
miR-215-5p could suppress ELOVL6expression in mouse3T3-L1adipocytes and miR-215-5p also could suppress ELOVL2and ELOVL6in mouse Hepa1-6hepatocytes by using Q-PCR. miR-135a may regulate fatty acid elongation.
In summary, the conclusions of this study are:①miR-224could suppress EGR2expression by directly targeting it and impair adipocyte differentiation during early adipogenesis; miR-224also could suppress ACSL4expression by directly targeting it and regulate fatty acid metabolism.②miR-146b could suppress Runxltl and Smad4expression by directly targeting them and promote adipocyte differentiation during early adipogenesis.③miR-215could suppress FNDC3B and CTNNBIP1expression by directly targeting them and impair adipocyte differentiation during early adipogenesis.④miR-135a may regulate fatty acid elongation.
引文
1.罗艳,张群,梁宇君,张士璀.动物中microRNA的保守性和进化历程.中国科学：生命科学,2012,02
2.季海峰,张沅.猪脂肪代谢的研究进展.中国畜牧杂志,1993,3
3.王海燕,苏玉虹.编码极长链脂肪酸延长酶基因家族的结构及其产物的功能.生命的化学,2005,25(1)
4. Aboobaker AA, Tomancak P, Patel N, Rubin GM, Lai EC. Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development. Proc Natl Acad Sci U S A, 2005,102: 18017-18022
5. Ahn J, Lee H, Jung CH, Jeon TI, Ha TY. MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade. EMBO Mol Med,2013,5:1602-1612
6. Akanbi KA, Mersmann HJ. Beta-adrenergic receptors in porcine adipocyte membranes:modification by animal age, depot site, and dietary protein deficiency. J Anim Sci,1996, 74:551-561
7. Alberti KG, Zimmet P, Shaw J. Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med, 2006, 23:469-480
8. Antonson P, Pray MG, Jacobsson A, Xanthopoulos KG. Myc inhibits CCAAT/enhancer-binding protein alpha-gene expression in HIB-1B hibernoma cells through interactions with the core promoter region. Eur J Biochem, 1995,232: 397-403
9. Ason B, Darnell DK, Wittbrodt B, Berezikov E, Kloosterman WP, Wittbrodt J, Antin PB, Plasterk RH. Differences in vertebrate microRNA expression. Proc Natl Acad Sci U S A, 2006,103:14385-14389
10. Attisano L, Wrana JL. Signal transduction by the TGF-beta superfamily. Science, 2002,296:1646-1647
11. Banerjee SS, Feinberg MW, Watanabe M, Gray S, Haspel RL, Denkinger DJ, Kawahara R, Hauner H, Jain MK. The Kruppel-like factor KLF2 inhibits peroxisome proliferator-activated receptor-gamma expression and adipogenesis. J Biol Chem, 2003,278:2581-2584
12. Bayarsaihan D. Epigenetic mechanisms in inflammation. J Dent Res, 2011,90:9-17
13. Bennett CN, Ross SE, Longo KA, Bajnok L, Hemati N, Johnson KW, Harrison SD, MacDougald OA. Regulation of Wnt signaling during adipogenesis. J Biol Chem, 2002,277:30998-31004
14. Berezikov E, Cuppen E, Plasterk RH. Approaches to microRNA discovery. Nat Genet,2006,38 Suppl:S2-7
15. Boguslawska J, Wojcicka A, Piekielko-Witkowska A, Master A, Nauman A. MiR-224 targets the 3'UTR of type 1 5'-iodothyronine deiodinase possibly contributing to tissue hypothyroidism in renal cancer. PLoS One, 2011, 6:e24541
16. Bonasio R, Tu S, Reinberg D. Molecular signals of epigenetic states. Science, 2010, 330:612-616
17. Bortell R, Owen TA, Ignotz R, Stein GS, Stein JL. TGF beta 1 prevents the down-regulation of type I procollagen, fibronectin, and TGF beta 1 gene expression associated with 3T3-L1 pre-adipocyte differentiation. J Cell Biochem, 1994, 54: 256-263
18. Braun CJ, Zhang X, Savelyeva I, Wolff S, Moll UM, Schepeler T, Orntoft TF, Andersen CL, Dobbelstein M. p53-Responsive micrornas 192 and 215 are capable of inducing cell cycle arrest. Cancer Res, 2008,68:10094-10104
19. Brun RP, Tontonoz P, Forman BM, Ellis R, Chen J, Evans RM, Spiegelman BM. Differential activation of adipogenesis by multiple PPAR isoforms. Genes Dev,1996, 10:974-984
20. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A, 2002, 99:15524-15529
21. Carrer M, Liu N, Grueter CE, Williams AH, Frisard MI, Hulver MW, Bassel-Duby R, Olson EN. Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*. Proc Natl Acad Sci U S A, 2012,109:15330-15335
22. Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, Xu C, Mason WS, Moloshok T, Bort R, Zaret KS, Taylor JM. miR-122, a mammalian liver-specific microRNA, is processed from her mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol, 2004, 1:106-113
23. Chen C, Deng B, Qiao M, Zheng R, Chai J, Ding Y, Peng J, Jiang S. Solexa sequencing identification of conserved and novel microRNAs in backfat of Large White and Chinese Meishan pigs. PLoS One,2012, 7:e31426
24. Chen C, Peng Y, Peng Y, Peng J, Jiang S. miR-135a-5p inhibits 3T3-L1 adipogenesis through activation of canonical Wnt/beta-catenin signaling. J Mol Endocrinol, 2014, 52:311-320
25. Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, Lao KQ, Livak KJ, Guegler KJ. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res, 2005,33: e179
26. Chen S, Sang N. Histone deacetylase inhibitors:the epigenetic therapeutics that repress hypoxia-inducible factors. Journal of biomedicine & biotechnology, 2011, 2011:197946-197946
27. Chen Z, Torrens JI, Anand A, Spiegelman BM, Friedman JM. Krox20 stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms. Cell Metab, 2005,1:93-106
28. Chou CK, Chen RF, Chou FF, Chang HW, Chen YJ, Lee YF, Yang KD, Cheng JT, Huang CC, Liu RT. miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF(V600E) mutation. Thyroid,2010,20:489-494
29. Choy L, Derynck R. Transforming growth factor-beta inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation function. J Biol Chem, 2003,278:9609-9619
30. Choy L, Skillington J, Derynck R. Roles of autocrine TGF-beta receptor and Smad signaling in adipocyte differentiation. J Cell Biol, 2000, 149:667-682
31. Christodoulides C, Lagathu C, Sethi JK, Vidal-Puig A. Adipogenesis and WNT signalling. Trends Endocrinol Metab, 2009,20:16-24
32. Christy RJ, Kaestner KH, Geiman DE, Lane MD. CCAAT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3-L1 preadipocytes. Proc Natl Acad Sci U S A,1991,88:2593-2597
33. Costa FF. Epigenomics in cancer management. Cancer Manag Res, 2010,2:255-265
34. Dalgliesh GL, Furge K, Greenman C, Chen L, Bignell G, Butler A, Davies H, Edkins S, Hardy C, Latimer C, Teague J, Andrews J, Barthorpe S, Beare D, Buck G, Campbell PJ, Forbes S, Jia M, Jones D, Knott H et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature, 2010,463: 360-363
35. Daniels DL, Weis WI. ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules. Mol Cell,2002,10:573-584
36. Davalos A, Goedeke L, Smibert P, Ramirez CM, Warrier NP, Andreo U, Cirera-Salinas D, Rayner K, Suresh U, Pastor-Pareja JC, Esplugues E, Fisher EA, Penalva LO, Moore KJ, Suarez Y, Lai EC, Fernandez-Hernando C. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc Natl Acad Sci U S A,2011,108:9232-9237
37. Davis KE, Moldes M, Farmer SR. The forkhead transcription factor FoxC2 inhibits white adipocyte differentiation. J Biol Chem, 2004,279: 42453-42461
38. Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet, 2001,29:117-129
39. Desvergne B, Wahli W. Peroxisome proliferator-activated receptors:nuclear control of metabolism. Endocr Rev, 1999,20:649-688
40. El-Jack AK, Hamm JK, Pilch PF, Farmer SR. Reconstitution of insulin-sensitive glucose transport in fibroblasts requires expression of both PPARgamma and C/EBPalpha. J Biol Chem, 1999,274:7946-7951
41. Enomoto H, Furuichi T, Zanma A, Yamana K, Yoshida C, Sumitani S, Yamamoto H, Enomoto-Iwamoto M, Iwamoto M, Komori T. Runx2 deficiency in chondrocytes causes adipogenic changes in vitro. J Cell Sci, 2004,117:417-425
42. Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS. MicroRNA targets in Drosophila. Genome Biol,2003,5:R1
43. Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, Watts L, Booten SL, Graham M, McKay R, Subramaniam A, Propp S, Lollo BA, Freier S, Bennett CF, Bhanot S, Monia BP. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab, 2006,3:87-98
44. Esau C, Kang X, Peralta E, Hanson E, Marcusson EG, Ravichandran LV, Sun Y, Koo S, Perera RJ, Jain R, Dean NM, Freier SM, Bennett CF, Lollo B, Griffey R. MicroRNA-143 regulates adipocyte differentiation. J Biol Chem, 2004, 279: 52361-52365
45. Farmer SR. Transcriptional control of adipocyte formation. Cell Metab, 2006, 4: 263-273
46. Feng XH, Derynck R. Specificity and versatility in tgf-beta signaling through Smads. Annu Rev Cell Dev Biol, 2005,21:659-693
47. Fernandez-Morera JL, Calvanese V, Rodriguez-Rodero S, Menendez-Torre E, Fraga MF. Epigenetic regulation of the immune system in health and disease. Tissue Antigens, 2010, 76: 431-439
48. Fernyhough ME, Okine E, Hausman G, Vierck JL, Dodson MV. PPARgamma and GLUT-4 expression as developmental regulators/markers for preadipocyte differentiation into an adipocyte. Domest Anim Endocrinol, 2007, 33:367-378
49. Flowers E, Froelicher ES, Aouizerat BE. MicroRNA regulation of lipid metabolism. Metabolism,2013,62:12-20
50. Freytag SO, Geddes TJ. Reciprocal regulation of adipogenesis by Myc and C/EBP alpha. Science,1992,256: 379-382
51. Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Research,2009,19:92-105
52. Fu M, Rao M, Bouras T, Wang C, Wu K, Zhang X, Li Z, Yao TP, Pestell RG Cyclin Dl inhibits peroxisome proliferator-activated receptor gamma-mediated adipogenesis through histone deacetylase recruitment. J Biol Chem,2005, 280: 16934-16941
53. Georges SA, Biery MC, Kim SY, Schelter JM, Guo J, Chang AN, Jackson AL, Carleton MO, Linsley PS, Cleary MA, Chau BN. Coordinated regulation of cell cycle transcripts by p53-Inducible microRNAs, miR-192 and miR-215. Cancer Res, 2008,68:10105-10112
54. Geraldo MV, Yamashita AS, Kimura ET. MicroRNA miR-146b-5p regulates signal transduction of TGF-beta by repressing SMAD4 in thyroid cancer. Oncogene,2012, 31:1910-1922
55. Gerin I, Bommer GT, McCoin CS, Sousa KM, Krishnan V, MacDougald OA. Roles for miRNA-378/378* in adipocyte gene expression and lipogenesis. Am J Physiol Endocrinol Metab,2010,299:E198-206
56. Gerin I, Clerbaux LA, Haumont O, Lanthier N, Das AK, Burant CF, Leclercq IA, MacDougald OA, Bommer GT. Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J Biol Chem, 2010, 285: 33652-33661
57. Gregoire FM, Smas CM, Sul HS. Understanding adipocyte differentiation. Physiol Rev, 1998,78:783-809
58. Guo Y, Chen Y, Zhang Y, Zhang Y, Chen L, Mo D. Up-regulated miR-145 expression inhibits porcine preadipocytes differentiation by targeting IRS1. Int J Biol Sci, 2012, 8:1408-1417
59. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW. Identification of c-MYC as a target of the APC pathway. Science,1998,281:1509-1512
60. Hilton C, Neville MJ, Karpe F. MicroRNAs in adipose tissue:their role in adipogenesis and obesity. Int J Obes (Lond),2013,37:325-332
61. Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene, 1989,77:51-59
62. Hoekstra M, van der Sluis RJ, Kuiper J, Van Berkel TJ. Nonalcoholic fatty liver disease is associated with an altered hepatocyte microRNA profile in LDL receptor knockout mice. J Nutr Biochem, 2012,23:622-628
63. Holmes A, Abraham DJ, Sa S, Shiwen X, Black CM, Leask A. CTGF and SMADs, maintenance of scleroderma phenotype is independent of SMAD signaling. J Biol Chem,2001,276:10594-10601
64. Huang J, Zhao L, Xing L, Chen D. MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells, 2010,28: 357-364
65. Huber LC, Stanczyk J, Jungel A, Gay S. Epigenetics in inflammatory rheumatic diseases. Arthritis Rheum,2007,56:3523-3531
66. Iliopoulos D, Drosatos K, Hiyama Y, Goldberg IJ, Zannis Ⅵ. MicroRNA-370 controls the expression of microRNA-122 and Cptlalpha and affects lipid metabolism. J Lipid Res,2010,51:1513-1523
67. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature,1990, 347:645-650
68. Jakobsson A, Westerberg R, Jacobsson A. Fatty acid elongases in mammals:their regulation and roles in metabolism. Prog Lipid Res,2006,45:237-249
69. Jia Z, Moulson CL, Pei Z, Miner JH, Watkins PA. Fatty acid transport protein 4 is the principal very long chain fatty acyl-CoA synthetase in skin fibroblasts. J Biol Chem,2007,282:20573-20583
70. Jing E, Gesta S, Kahn CR. SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. Cell Metab, 2007,6: 105-114
71. Karbiener M, Fischer C, Nowitsch S, Opriessnig P, Papak C, Ailhaud G, Dani C, Amri EZ, Scheideler M. microRNA miR-27b impairs human adipocyte differentiation and targets PPARgamma. Biochem Biophys Res Commun,2009,390: 247-251
72. Karbiener M, Neuhold C, Opriessnig P, Prokesch A, Bogner-Strauss JG, Scheideler M. MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1 and ALK2. RNA Biol,2011,8:850-860
73. Kennell JA, Gerin I, MacDougald OA, Cadigan KM. The microRNA miR-8 is a conserved negative regulator of Wnt signaling. Proc Natl Acad Sci U S A,2008,105: 15417-15422
74. Kennell JAG, I.;MacDougald, O. A.;Cadigan, K. M. The microRNA miR-8 is a conserved negative regulator of Wnt signaling. Proc Natl Acad Sci U S A, 2008,105: 15417-15422
75. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. Journal Of Clinical Endocrinology & Metabolism,2004,89:2548-2556
76. Killenberg PG, Davidson ED, Webster LT, Jr. Evidence for a medium-chain fatty acid: coenzyme A ligase (adenosine monophosphate) that activates salicylate. Mol Pharmacol,1971,7:260-268
77. Kim JB, Wright HM, Wright M, Spiegelman BM. ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand. Proc Natl Acad Sci U S A,1998,95:4333-4337
78. Kim SY, Kim AY, Lee HW, Son YH, Lee GY, Lee JW, Lee YS, Kim JB. miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression. Biochem Biophys Res Commun, 2010,392:323-328
79. Kim YJ, Hwang SH, Cho HH, Shin KK, Bae YC, Jung JS. MicroRNA 21 regulates the proliferation of human adipose tissue-derived mesenchymal stem cells and high-fat diet-induced obesity alters microRNA 21 expression in white adipose tissues. J Cell Physiol, 2012,227: 183-193
80. Kim YJ, Hwang SJ, Bae YC, Jung JS. MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue. Stem Cells,2009,27:3093-3102
81. Kinoshita M, Ono K, Horie T, Nagao K, Nishi H, Kuwabara Y, Takanabe-Mori R, Hasegawa K, Kita T, Kimura T. Regulation of adipocyte differentiation by activation of serotonin (5-HT) receptors 5-HT2AR and 5-HT2CR and involvement of microRNA-448-mediated repression of KLF5. Mol Endocrinol, 2010, 24:1978-1987
82. Kloosterman WP, Wienholds E, de Bruijn E, Kauppinen S, Plasterk RH. In situ detection of miRNAs in animal embryos using LNA-modified oligonucleotide probes. Nat Methods,2006,3:27-29
83. Kobayashi T, Zadravec D, Jacobsson A. ELOVL2 overexpression enhances triacylglycerol synthesis in 3T3-L1 and F442A cells. FEBS Lett, 2007, 581: 3157-3163
84. Konig B, Koch A, Spielmann J, Hilgenfeld C, Stangl GI, Eder K. Activation of PPARalpha lowers synthesis and concentration of cholesterol by reduction of nuclear SREBP-2. Biochem Pharmacol,2007,73:574-585
85. Koolman J, Rohm KH. Color atlas of biochemistry. Thieme; 2005.
86. Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N. Combinatorial microRNA target predictions. Nat Genet,2005,37:495-500
87. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol,2002,12: 735-739
88. Laiho M, DeCaprio JA, Ludlow JW, Livingston DM, Massague J. Growth inhibition by TGF-beta linked to suppression of retinoblastoma protein phosphorylation. Cell, 1990,62:175-185
89. Landschulz WH, Johnson PF, Adashi EY, Graves BJ, McKnight SL. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev, 1988,2:786-800
90. Leask A, Holmes A, Black CM, Abraham DJ. Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in fibroblasts. J Biol Chem,2003,278:13008-13015
91. Lee EK, Lee MJ, Abdelmohsen K, Kim W, Kim MM, Srikantan S, Martindale JL, Hutchison ER, Kim HH, Marasa BS, Selimyan R, Egan JM, Smith SR, Fried SK, Gorospe M. miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression. Mol Cell Biol, 2011,31:626-638
92. Lee JC, Zhao JT, Clifton-Bligh RJ, Gill A, Gundara JS, Ip JC, Glover A, Sywak MS, Delbridge LW, Robinson BG, Sidhu SB. MicroRNA-222 and MicroRNA-146b Are Tissue and Circulating Biomarkers of Recurrent Papillary Thyroid Cancer. Cancer, 2013,119:4358-4365
93. Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science,2001,294:862-864
94. Lee RC, Gowrishankar TR, Basch RM, Patel PK, Golan DE. Cell shape-dependent rectification of surface receptor transport in a sinusoidal electric field. Biophys J, 1993,64:44-57
95. Lee SL, Sadovsky Y, Swirnoff AH, Polish JA, Goda P, Gavrilina G, Milbrandt J. Luteinizing hormone deficiency and female infertility in mice lacking the transcription factor NGFI-A(Egr-l). Science, 1996,273:1219-1221
96. Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J,2002,21:4663-4670
97. Lefterova MI, Lazar MA. New developments in adipogenesis. Trends Endocrinol Metab,2009,20:107-114
98. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 2005,120:15-20
99. Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell,2003,115:787-798
100. Li MO, Flavell RA. TGF-beta: a master of all T cell trades. Cell, 2008,134:392-404
101. Li S, Gao J, Gu J, Yuan J, Hua D, Shen L. MicroRNA-215 inhibits relapse of colorectal cancer patients following radical surgery. Medical Oncology, 2013,30:
102. Liao WT, Li TT, Wang ZG, Wang SY, He MR, Ye YP, Qi L, Cui YM, Wu P, Jiao HL, Zhang C, Xie YJ, Wang JX, Ding YQ. microRNA-224 promotes cell proliferation and tumor growth in human colorectal cancer by repressing PHLPP1 and PHLPP2. Clin Cancer Res,2013,19:4662-4672
103. Lin FT, Lane MD. CCAAT/enhancer binding protein alpha is sufficient to initiate the 3T3-L1 adipocyte differentiation program. Proc Natl Acad Sci U S A, 1994, 91: 8757-8761
104. Lin Q, Gao Z, Alarcon RM, Ye J, Yun Z. A role of miR-27 in the regulation of adipogenesis. FEBS J, 2009,276:2348-2358
105. Ling HY, Wen GB, Feng SD, Tuo QH, Ou HS, Yao CH, Zhu BY, Gao ZP, Zhang L, Liao DF. MicroRNA-375 promotes 3T3-L1 adipocyte differentiation through modulation of extracellular signal-regulated kinase signalling. Clin Exp Pharmacol Physiol, 2011,38:239-246
106. Linhart HG, Ishimura-Oka K, DeMayo F, Kibe T, Repka D, Poindexter B, Bick RJ, Darlington GJ. C/EBPalpha is required for differentiation of white, but not brown, adipose tissue. Proc Natl Acad Sci U S A, 2001,98:12532-12537
107. Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M, Dumitru CD, Shimizu M, Zupo S, Dono M, Alder H, Bullrich F, Negrini M, Croce CM. An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci U S A, 2004,101:9740-9744
108. Liu S, Yang Y, Wu J. TNFalpha-induced up-regulation of miR-155 inhibits adipogenesis by down-regulating early adipogenic transcription factors. Biochem Biophys Res Commun, 2011,414:618-624
109. Lonn P, Moren A, Raja E, Dahl M, Moustakas A. Regulating the stability of TGFbeta receptors and Smads. Cell Res, 2009, 19:21-35
110. Lowe CE, O'Rahilly S, Rochford JJ. Adipogenesis at a glance. Journal Of Cell Science,2011,124:2681-2686
111. Lowe CE, O'Rahilly S, Rochford JJ. Adipogenesis at a glance. J Cell Sci, 2011,124: 2681-2686
112. Lu J, Fu Y, Kumar S, Shen Y, Zeng K, Xu A, Carthew R, Wu CI. Adaptive evolution of newly emerged micro-RNA genes in Drosophila. Mol Biol Evol, 2008,25: 929-938
113. Luquet S, Gaudel C, Holst D, Lopez-Soriano J, Jehl-Pietri C, Fredenrich A, Grimaldi PA. Roles of PPAR delta in lipid absorption and metabolism: a new target for the treatment of type 2 diabetes. Biochim Biophys Acta, 2005, 1740: 313-317
114. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling:components, mechanisms, and diseases. Dev Cell,2009,17:9-26
115. MacDougald OA, Lane MD. Transcriptional regulation of gene expression during adipocyte differentiation. Annu Rev Biochem, 1995,64:345-373
116. Mann B, Gelos M, Siedow A, Hanski ML, Gratchev A, Ilyas M, Bodmer WF, Moyer MP, Riecken EO, Buhr HJ, Hanski C. Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci U S A,1999,96:1603-1608
117. Marquart TJ, Allen RM, Ory DS, Baldan A. miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci U S A, 2010,107:12228-12232
118. Martinelli R, Nardelli C, Pilone V, Buonomo T, Liguori R, Castano I, Buono P, Masone S, Persico G, Forestieri P, Pastore L, Sacchetti L. miR-519d overexpression is associated with human obesity. Obesity (Silver Spring), 2010, 18:2170-2176
119. Mashek DG, Bornfeldt KE, Coleman RA, Berger J, Bernlohr DA, Black P, DiRusso CC, Farber SA, Guo W, Hashimoto N, Khodiyar V, Kuypers FA, Maltais LJ, Nebert DW, Renieri A, Schaffer JE, Stahl A, Watkins PA, Vasiliou V, Yamamoto TT. Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family. J Lipid Res, 2004,45:1958-1961
120. Massague J, Blain SW, Lo RS. TGFbeta signaling in growth control, cancer, and heritable disorders. Cell, 2000,103:295-309
121.Mees ST, Mardin WA, Sielker S, Willscher E, Senninger N, Schleicher C, Colombo-Benkmann M, Haier J. Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas. Ann Surg Oncol, 2009,16:2339-2350
122. Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B, Rigoutsos I. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell, 2006,126:1203-1217
123. Miyanari Y, Torres-Padilla ME. Epigenetic regulation of reprogramming factors towards pluripotency in mouse preimplantation development. Curr Opin Endocrinol Diabetes Obes,2010,17:500-506
124. Moon YA, Shah NA, Mohapatra S, Warrington JA, Horton JD. Identification of a mammalian long chain fatty acyl elongase regulated by sterol regulatory element-binding proteins. J Biol Chem, 2001,276:45358-45366
125. Mori T, Sakaue H, Iguchi H, Gomi H, Okada Y, Takashima Y, Nakamura K, Nakamura T, Yamauchi T, Kubota N, Kadowaki T, Matsuki Y, Ogawa W, Hiramatsu R, Kasuga M. Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J Biol Chem, 2005,280:12867-12875
126. Mulligan C, Rochford J, Denyer G, Stephens R, Yeo G, Freeman T, Siddle K, O'Rahilly S. Microarray analysis of insulin and insulin-like growth factor-1 (IGF-1) receptor signaling reveals the selective up-regulation of the mitogen heparin-binding EGF-like growth factor by IGF-1. J Biol Chem, 2002,277:42480-42487
127. Nagel R, le Sage C, Diosdado B, van der Waal M, Oude Vrielink JA, Bolijn A, Meijer GA, Agami R. Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer. Cancer Res, 2008,68:5795-5802
128. Najafi-Shoushtari SH, Kristo F, Li Y, Shioda T, Cohen DE, Gerszten RE, Naar AM. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science,2010,328:1566-1569
129. Nakachi Y, Yagi K, Nikaido I, Bono H, Tonouchi M, Schonbach C, Okazaki Y. Identification of novel PPARgamma target genes by integrated analysis of ChlP-on-chip and microarray expression data during adipocyte differentiation. Biochem Biophys Res Commun, 2008,372:362-366
130. Nakanishi N, Nakagawa Y, Tokushige N, Aoki N, Matsuzaka T, Ishii K, Yahagi N, Kobayashi K, Yatoh S, Takahashi A, Suzuki H, Urayama O, Yamada N, Shimano H. The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice. Biochem Biophys Res Commun, 2009,385:492-496
131.Navarro A, Diaz T, Martinez A, Gaya A, Pons A, Gel B, Codony C, Ferrer G, Martinez C, Montserrat E, Monzo M. Regulation of JAK2 by miR-135a:prognostic impact in classic Hodgkin lymphoma. Blood,2009,114:2945-2951
132. Ntambi JM, Young-Cheul K. Adipocyte differentiation and gene expression. J Nutr, 2000,130:3122S-3126S
133. Oishi Y, Manabe I, Tobe K, Tsushima K, Shindo T, Fujiu K, Nishimura G, Maemura K, Yamauchi T, Kubota N, Suzuki R, Kitamura T, Akira S, Kadowaki T, Nagai R. Kruppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation. Cell Metab,2005,1:27-39
134. Oller do Nascimento CM, Ribeiro EB, Oyama LM. Metabolism and secretory function of white adipose tissue:effect of dietary fat. An Acad Bras Cienc, 2009,81: 453-466
135. Ospelt C, Reedquist KA, Gay S, Tak PP. Inflammatory memories:is epigenetics the missing link to persistent stromal cell activation in rheumatoid arthritis? Autoimmun Rev, 2011,10:519-524
136. Otto TC, Lane MD. Adipose development:from stem cell to adipocyte. Crit Rev Biochem Mol Biol,2005,40:229-242
137. Ou Z, Wada T, Gramignoli R, Li S, Strom SC, Huang M, Xie W. MicroRNA hsa-miR-613 targets the human LXRalpha gene and mediates a feedback loop of LXRalpha autoregulation. Mol Endocrinol,2011,25:584-596
138. Pang RTK, Liu W-M, Leung CON, Ye T-M, Kwan PCK, Lee K-F, Yeung WSB. miR-135A Regulates Preimplantation Embryo Development through Down-Regulation of E3 Ubiquitin Ligase Seven in Absentia Homolog 1A(SIAH1A) Expression. Plos One, 2011,6:
139. Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Muller P, Spring J, Srinivasan A, Fishman M, Finnerty J, Corbo J, Levine M, Leahy P, Davidson E, Ruvkun G. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature, 2000,408:86-89
140. Patnaik SK, Kannisto E, Mallick R, Yendamuri S. Overexpression of the lung cancer-prognostic miR-146b microRNAs has a minimal and negative effect on the malignant phenotype of A549 lung cancer cells. PLoS One, 2011,6:e22379
141. Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L. Sirtl promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature, 2004,429:771-776
142. Prestwich TC, Macdougald OA. Wnt/beta-catenin signaling in adipogenesis and metabolism. Curr Opin Cell Biol, 2007,19:612-617
143. Qin L, Chen Y, Niu Y, Chen W, Wang Q, Xiao S, Li A, Xie Y, Li J, Zhao X, He Z, Mo D. A deep investigation into the adipogenesis mechanism: profile of microRNAs regulating adipogenesis by modulating the canonical Wnt/beta-catenin signaling pathway. BMC Genomics,2010,11:320
144. Rahimi N, Tremblay E, McAdam L, Roberts A, Elliott B. Autocrine secretion of TGF-beta 1 and TGF-beta 2 by pre-adipocytes and adipocytes:a potent negative regulator of adipocyte differentiation and proliferation of mammary carcinoma cells. In Vitro Cell Dev Biol Anim, 1998,34:412-420
145. Rakyan V, Whitelaw E. Transgenerational epigenetic inheritance. Curr Biol, 2003, 13:R6
146. Ramirez CM, Davalos A, Goedeke L, Salerno AG, Warrier N, Cirera-Salinas D, Suarez Y, Fernandez-Hernando C. MicroRNA-758 regulates cholesterol efflux through posttranscriptional repression of ATP-binding cassette transporter Al. Arterioscler Thromb Vase Biol,2011,31:2707-2714
147. Ramji DP, Foka P. CCAAT/enhancer-binding proteins:structure, function and regulation. Biochem J, 2002,365:561-575
148. Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE, Parathath S, van Gils JM, Rayner AJ, Chang AN, Suarez Y, Fernandez-Hernando C, Fisher EA, Moore KJ. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J Clin Invest,2011,121:2921-2931
149. Rayner KJ, Suarez Y, Davalos A, Parathath S, Fitzgerald ML, Tamehiro N, Fisher EA, Moore KJ, Fernandez-Hernando C. MiR-33 contributes to the regulation of cholesterol homeostasis. Science,2010,328:1570-1573
150. Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R. Fast and effective prediction of microRNA/target duplexes. RNA,2004, 10: 1507-1517
151. Richardson RL, Campion DR, Hausman GJ, Wright JT. Transforming growth factor type beta (TGF-beta) and adipogenesis in pigs. Journal of animal science, 1989,67: 2171-2180
152. Rochford JJ, Semple RK, Laudes M, Boyle KB, Christodoulides C, Mulligan C, Lelliott CJ, Schinner S, Hadaschik D, Mahadevan M, Sethi JK, Vidal-Puig A, O'Rahilly S. ETO/MTG8 is an inhibitor of C/EBPbeta activity and a regulator of early adipogenesis. Mol Cell Biol,2004,24:9863-9872
153. Rodriguez-Rodero S, Fernandez-Morera JL, Fernandez AF, Menendez-Torre E, Fraga MF. Epigenetic regulation of aging. Discovery medicine, 2010, 10:225-233
154. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian micro RNA host genes and transcription units. Genome Res, 2004, 14: 1902-1910
155. Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ, Spiegelman BM. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes Dev,2002,16:22-26
156. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev,2000,14:1293-1307
157. Ross S, Hill CS. How the Smads regulate transcription. International Journal Of Biochemistry & Cell Biology, 2008,40:383-408
158. Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL, MacDougald OA. Inhibition of adipogenesis by Wnt signaling. Science,2000,289:950-953
159. Ruvkun G. Molecular biology. Glimpses of a tiny RNA world. Science, 2001,294: 797-799
160. Salma N, Xiao H, Imbalzano AN. Temporal recruitment of CCAAT/enhancer-binding proteins to early and late adipogenic promoters in vivo. J Mol Endocrinol,2006,36:139-151
161. Schmierer B, Hill CS. TGFbeta-SMAD signal transduction:molecular specificity and functional flexibility. Nat Rev Mol Cell Biol, 2007,8: 970-982
162. Schneider-Maunoury S, Topilko P, Seitandou T, Levi G, Cohen-Tannoudji M, Pournin S, Babinet C, Charnay P. Disruption of Krox-20 results in alteration of rhombomeres 3 and 5 in the developing hindbrain. Cell,1993,75:1199-1214
163. Scisciani C, Vossio S, Guerrieri F, Schinzari V, De Iaco R, D'Onorio de Meo P, Cervello M, Montalto G, Pollicino T, Raimondo G, Levrero M, Pediconi N. Transcriptional regulation of miR-224 upregulated in human HCCs by NFkappaB inflammatory pathways. J Hepatol, 2012,56:855-861
164.Shi R, Sun YH, Zhang XH, Chiang VL. Poly(T) adaptor RT-PCR. Methods Mol Biol, 2012,822:53-66
165. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell, 2003,113:685-700
166. Shi Y, Wang YF, Jayaraman L, Yang H, Massague J, Pavletich NP. Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling. Cell,1998,94:585-594
167. Shtutman M, Zhurinsky J, Simcha I, Albanese C, D'Amico M, Pestell R, Ben-Ze'ev A. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad SciU S A,1999,96: 5522-5527
168. Shulman AI, Mangelsdorf DJ. Retinoid x receptor heterodimers in the metabolic syndrome. N Engl J Med, 2005,353:604-615
169. Song B, Wang Y, Titmus MA, Botchkina G, Formentini A, Kornmann M, Ju J. Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells. Mol Cancer,2010,9:96
170. Soupene E, Kuypers FA. Mammalian long-chain acyl-CoA synthetases. Exp Biol Med (Maywood),2008,233:507-521
171. Sparks RL, Allen BJ, Strauss EE. TGF-beta blocks early but not late differentiation-specific gene expression and morphologic differentiation of 3T3 T proadipocytes. J Cell Physiol, 1992,150:568-577
172. Sun T, Fu M, Bookout AL, Kliewer SA, Mangelsdorf DJ. MicroRNA let-7 regulates 3T3-L1 adipogenesis. Mol Endocrinol,2009,23:925-931
173. Swiatek PJ, Gridley T. Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20. Genes Dev, 1993,7:2071-2084
174. Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of micro RNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A,2006, 103:12481-12486
175. Tago K, Nakamura T, Nishita M, Hyodo J, Nagai S, Murata Y, Adachi S, Ohwada S, Morishita Y, Shibuya H, Akiyama T. Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein. Genes Dev,2000,14:1741-1749
176. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res,2004,64:3753-3756
177.Takanabe R, Ono K, Abe Y, Takaya T, Horie T, Wada H, Kita T, Satoh N, Shimatsu A, Hasegawa K. Up-regulated expression of micro RNA-143 in association with obesity in adipose tissue of mice fed high-fat diet. Biochem Biophys Res Commun, 2008, 376:728-732
178. Tan JT, McLennan SV, Song WW, Lo LW, Bonner JG, Williams PF, Twigg SM. Connective tissue growth factor inhibits adipocyte differentiation. Am J Physiol Cell Physiol,2008,295:C740-751
179. Tanaka T, Yoshida N, Kishimoto T, Akira S. Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene. EMBO J,1997,16:7432-7443
180. Tang W-w, Wan G-p, Wan Y-c, Zhang L, Cheng W-j. Effects of miR-135a on HOXA10 expression, proliferation and apoptosis of ovarian cancer cells. Zhonghua fu chan ke za zhi, 2013,48:364-369
181. Taylor AW. Review of the activation of TGF-beta in immunity. J Leukoc Biol, 2009, 85:29-33
182. Teleman AA, Maitra S, Cohen SM. Drosophila lacking microRNA miR-278 are defective in energy homeostasis. Genes Dev,2006,20:417-422
183. Teran-Garcia M, Bouchard C. Genetics of the metabolic syndrome. Appl Physiol Nutr Metab,2007,32:89-114
184. Tetsu O, McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature,1999,398:422-426
185. Tominaga K, Kondo C, Johmura Y, Nishizuka M, Imagawa M. The novel gene fad104, containing a fibronectin type III domain, has a significant role in adipogenesis. FEBS Lett,2004,577:49-54
186. Tong Q, Tsai J, Tan G, Dalgin G, Hotamisligil GS. Interaction between GATA and the C/EBP family of transcription factors is critical in GATA-mediated suppression of adipocyte differentiation. Mol Cell Biol,2005,25:706-715
187. Tontonoz P, Spiegelman BM. Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem,2008,77:289-312
188. Topilko P, Schneider-Maunoury S, Levi G, Baron-Van Evercooren A, Chennoufi AB, Seitanidou T, Babinet C, Charnay P. Krox-20 controls myelination in the peripheral nervous system. Nature, 1994,371:796-799
189. Torti FM, Torti SV, Larrick JW, Ringold GM. Modulation of adipocyte differentiation by tumor necrosis factor and transforming growth factor beta. J Cell Biol,1989,108:1105-1113
190. Tourtellotte WG, Milbrandt J. Sensory ataxia and muscle spindle agenesis in mice lacking the transcription factor Egr3. Nat Genet,1998,20:87-91
191. Waddington CH. The epigenotype. 1942. Int J Epidemiol,2012,41:10-13
192. Wang Q, Li YC, Wang J, Kong J, Qi Y, Quigg RJ, Li X. miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/pl30. Proc Natl Acad Sci U S A, 2008,105:2889-2894
193. Wang Y, Lee AT, Ma JZ, Wang J, Ren J, Yang Y, Tantoso E, Li KB, Ooi LL, Tan P, Lee CG Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regulation and apoptosis inhibitor-5 as a microRNA-224-specific target. J Biol Chem, 2008,283:13205-13215
194. Whitman M. Smads and early developmental signaling by the TGFbeta superfamily. Genes Dev,1998,12:2445-2462
195. Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E, Horvitz HR, Kauppinen S, Plasterk RH. MicroRNA expression in zebrafish embryonic development. Science, 2005,309:310-311
196. Williams AH, Liu N, van Rooij E, Olson EN. MicroRNA control of muscle development and disease. Curr Opin Cell Biol, 2009,21:461-469
197. Wu Z, Bucher NL, Farmer SR. Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids. Mol Cell Biol, 1996,16: 4128-4136
198. Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, McKeon C, Darlington GJ, Spiegelman BM. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell, 1999,3: 151-158
199. Wu Z, Xie Y, Bucher NL, Farmer SR. Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. Genes Dev, 1995,9:2350-2363
200. Xia H, Qi Y, Ng SS, Chen X, Li D, Chen S, Ge R, Jiang S, Li G, Chen Y, He ML, Kung HF, Lai L, Lin MC. microRNA-146b inhibits glioma cell migration and invasion by targeting MMPs. Brain Res,2009,1269:158-165
201. Xie H, Lim B, Lodish HF. MicroRNAs Induced During Adipogenesis that Accelerate Fat Cell Development Are Downregulated in Obesity. Diabetes, 2009, 58:1050-1057
202. Xu P-F, Houssin N, Ferri-Lagneau KF, Thisse B, Thisse C. Construction of a Vertebrate Embryo from Two Opposing Morphogen Gradients. Science,2014,344: 87-89
203. Xu P, Vernooy SY, Guo M, Hay BA. The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol, 2003,13:790-795
204. Xu PV, S. Y.;Guo, M.;Hay, B. A. The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol, 2003,13:790-795
205. Yang Z, Bian C, Zhou H, Huang S, Wang S, Liao L, Zhao RC. MicroRNA hsa-miR-138 inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells through adenovirus EID-1. Stem Cells Dev, 2011,20: 259-267
206. Yang Z, Ebright YW, Yu B, Chen X. HEN1 recognizes 21-24 nt small RNA duplexes and deposits a methyl group onto the 2' OH of the 3'terminal nucleotide. Nucleic Acids Res,2006,34:667-675
207. Zaragosi LE, Wdziekonski B, Brigand KL, Villageois P, Mari B, Waldmann R, Dani C, Barbry P. Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis. Genome Biol,2011,12:R64
208.Zhang L, Hou D, Chen X, Li D, Zhu L, Zhang Y, Li J, Bian Z, Liang X, Cai X, Yin Y, Wang C, Zhang T, Zhu D, Zhang D, Xu J, Chen Q, Ba Y, Liu J, Wang Q et al. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res,2012,22:107-126
209. Zheng L, Lv GC, Sheng J, Yang YD. Effect of miRNA-l0b in regulating cellular steatosis level by targeting PPAR-alpha expression, a novel mechanism for the pathogenesis of NAFLD. J Gastroenterol Hepatol,2010,25:156-163
210. Zizola CF, Frey SK, Jitngarmkusol S, Kadereit B, Yan N, Vogel S. Cellular retinol-binding protein type I (CRBP-I) regulates adipogenesis. Mol Cell Biol,2010, 30:3412-3420
211.Zuo Y, Qiang L, Farmer SR. Activation of CCAAT/enhancer-binding protein (C/EBP) alpha expression by C/EBP beta during adipogenesis requires a peroxisome proliferator-activated receptor-gamma-associated repression of HDAC1 at the C/ebp alpha gene promoter. J Biol Chem, 2006,281:7960-7967
2.季海峰,张沅.猪脂肪代谢的研究进展.中国畜牧杂志,1993,3
3.王海燕,苏玉虹.编码极长链脂肪酸延长酶基因家族的结构及其产物的功能.生命的化学,2005,25(1)
4. Aboobaker AA, Tomancak P, Patel N, Rubin GM, Lai EC. Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development. Proc Natl Acad Sci U S A, 2005,102: 18017-18022
5. Ahn J, Lee H, Jung CH, Jeon TI, Ha TY. MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade. EMBO Mol Med,2013,5:1602-1612
6. Akanbi KA, Mersmann HJ. Beta-adrenergic receptors in porcine adipocyte membranes:modification by animal age, depot site, and dietary protein deficiency. J Anim Sci,1996, 74:551-561
7. Alberti KG, Zimmet P, Shaw J. Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med, 2006, 23:469-480
8. Antonson P, Pray MG, Jacobsson A, Xanthopoulos KG. Myc inhibits CCAAT/enhancer-binding protein alpha-gene expression in HIB-1B hibernoma cells through interactions with the core promoter region. Eur J Biochem, 1995,232: 397-403
9. Ason B, Darnell DK, Wittbrodt B, Berezikov E, Kloosterman WP, Wittbrodt J, Antin PB, Plasterk RH. Differences in vertebrate microRNA expression. Proc Natl Acad Sci U S A, 2006,103:14385-14389
10. Attisano L, Wrana JL. Signal transduction by the TGF-beta superfamily. Science, 2002,296:1646-1647
11. Banerjee SS, Feinberg MW, Watanabe M, Gray S, Haspel RL, Denkinger DJ, Kawahara R, Hauner H, Jain MK. The Kruppel-like factor KLF2 inhibits peroxisome proliferator-activated receptor-gamma expression and adipogenesis. J Biol Chem, 2003,278:2581-2584
12. Bayarsaihan D. Epigenetic mechanisms in inflammation. J Dent Res, 2011,90:9-17
13. Bennett CN, Ross SE, Longo KA, Bajnok L, Hemati N, Johnson KW, Harrison SD, MacDougald OA. Regulation of Wnt signaling during adipogenesis. J Biol Chem, 2002,277:30998-31004
14. Berezikov E, Cuppen E, Plasterk RH. Approaches to microRNA discovery. Nat Genet,2006,38 Suppl:S2-7
15. Boguslawska J, Wojcicka A, Piekielko-Witkowska A, Master A, Nauman A. MiR-224 targets the 3'UTR of type 1 5'-iodothyronine deiodinase possibly contributing to tissue hypothyroidism in renal cancer. PLoS One, 2011, 6:e24541
16. Bonasio R, Tu S, Reinberg D. Molecular signals of epigenetic states. Science, 2010, 330:612-616
17. Bortell R, Owen TA, Ignotz R, Stein GS, Stein JL. TGF beta 1 prevents the down-regulation of type I procollagen, fibronectin, and TGF beta 1 gene expression associated with 3T3-L1 pre-adipocyte differentiation. J Cell Biochem, 1994, 54: 256-263
18. Braun CJ, Zhang X, Savelyeva I, Wolff S, Moll UM, Schepeler T, Orntoft TF, Andersen CL, Dobbelstein M. p53-Responsive micrornas 192 and 215 are capable of inducing cell cycle arrest. Cancer Res, 2008,68:10094-10104
19. Brun RP, Tontonoz P, Forman BM, Ellis R, Chen J, Evans RM, Spiegelman BM. Differential activation of adipogenesis by multiple PPAR isoforms. Genes Dev,1996, 10:974-984
20. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A, 2002, 99:15524-15529
21. Carrer M, Liu N, Grueter CE, Williams AH, Frisard MI, Hulver MW, Bassel-Duby R, Olson EN. Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*. Proc Natl Acad Sci U S A, 2012,109:15330-15335
22. Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, Xu C, Mason WS, Moloshok T, Bort R, Zaret KS, Taylor JM. miR-122, a mammalian liver-specific microRNA, is processed from her mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol, 2004, 1:106-113
23. Chen C, Deng B, Qiao M, Zheng R, Chai J, Ding Y, Peng J, Jiang S. Solexa sequencing identification of conserved and novel microRNAs in backfat of Large White and Chinese Meishan pigs. PLoS One,2012, 7:e31426
24. Chen C, Peng Y, Peng Y, Peng J, Jiang S. miR-135a-5p inhibits 3T3-L1 adipogenesis through activation of canonical Wnt/beta-catenin signaling. J Mol Endocrinol, 2014, 52:311-320
25. Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, Lao KQ, Livak KJ, Guegler KJ. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res, 2005,33: e179
26. Chen S, Sang N. Histone deacetylase inhibitors:the epigenetic therapeutics that repress hypoxia-inducible factors. Journal of biomedicine & biotechnology, 2011, 2011:197946-197946
27. Chen Z, Torrens JI, Anand A, Spiegelman BM, Friedman JM. Krox20 stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms. Cell Metab, 2005,1:93-106
28. Chou CK, Chen RF, Chou FF, Chang HW, Chen YJ, Lee YF, Yang KD, Cheng JT, Huang CC, Liu RT. miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF(V600E) mutation. Thyroid,2010,20:489-494
29. Choy L, Derynck R. Transforming growth factor-beta inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation function. J Biol Chem, 2003,278:9609-9619
30. Choy L, Skillington J, Derynck R. Roles of autocrine TGF-beta receptor and Smad signaling in adipocyte differentiation. J Cell Biol, 2000, 149:667-682
31. Christodoulides C, Lagathu C, Sethi JK, Vidal-Puig A. Adipogenesis and WNT signalling. Trends Endocrinol Metab, 2009,20:16-24
32. Christy RJ, Kaestner KH, Geiman DE, Lane MD. CCAAT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3-L1 preadipocytes. Proc Natl Acad Sci U S A,1991,88:2593-2597
33. Costa FF. Epigenomics in cancer management. Cancer Manag Res, 2010,2:255-265
34. Dalgliesh GL, Furge K, Greenman C, Chen L, Bignell G, Butler A, Davies H, Edkins S, Hardy C, Latimer C, Teague J, Andrews J, Barthorpe S, Beare D, Buck G, Campbell PJ, Forbes S, Jia M, Jones D, Knott H et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature, 2010,463: 360-363
35. Daniels DL, Weis WI. ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules. Mol Cell,2002,10:573-584
36. Davalos A, Goedeke L, Smibert P, Ramirez CM, Warrier NP, Andreo U, Cirera-Salinas D, Rayner K, Suresh U, Pastor-Pareja JC, Esplugues E, Fisher EA, Penalva LO, Moore KJ, Suarez Y, Lai EC, Fernandez-Hernando C. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc Natl Acad Sci U S A,2011,108:9232-9237
37. Davis KE, Moldes M, Farmer SR. The forkhead transcription factor FoxC2 inhibits white adipocyte differentiation. J Biol Chem, 2004,279: 42453-42461
38. Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet, 2001,29:117-129
39. Desvergne B, Wahli W. Peroxisome proliferator-activated receptors:nuclear control of metabolism. Endocr Rev, 1999,20:649-688
40. El-Jack AK, Hamm JK, Pilch PF, Farmer SR. Reconstitution of insulin-sensitive glucose transport in fibroblasts requires expression of both PPARgamma and C/EBPalpha. J Biol Chem, 1999,274:7946-7951
41. Enomoto H, Furuichi T, Zanma A, Yamana K, Yoshida C, Sumitani S, Yamamoto H, Enomoto-Iwamoto M, Iwamoto M, Komori T. Runx2 deficiency in chondrocytes causes adipogenic changes in vitro. J Cell Sci, 2004,117:417-425
42. Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS. MicroRNA targets in Drosophila. Genome Biol,2003,5:R1
43. Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, Watts L, Booten SL, Graham M, McKay R, Subramaniam A, Propp S, Lollo BA, Freier S, Bennett CF, Bhanot S, Monia BP. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab, 2006,3:87-98
44. Esau C, Kang X, Peralta E, Hanson E, Marcusson EG, Ravichandran LV, Sun Y, Koo S, Perera RJ, Jain R, Dean NM, Freier SM, Bennett CF, Lollo B, Griffey R. MicroRNA-143 regulates adipocyte differentiation. J Biol Chem, 2004, 279: 52361-52365
45. Farmer SR. Transcriptional control of adipocyte formation. Cell Metab, 2006, 4: 263-273
46. Feng XH, Derynck R. Specificity and versatility in tgf-beta signaling through Smads. Annu Rev Cell Dev Biol, 2005,21:659-693
47. Fernandez-Morera JL, Calvanese V, Rodriguez-Rodero S, Menendez-Torre E, Fraga MF. Epigenetic regulation of the immune system in health and disease. Tissue Antigens, 2010, 76: 431-439
48. Fernyhough ME, Okine E, Hausman G, Vierck JL, Dodson MV. PPARgamma and GLUT-4 expression as developmental regulators/markers for preadipocyte differentiation into an adipocyte. Domest Anim Endocrinol, 2007, 33:367-378
49. Flowers E, Froelicher ES, Aouizerat BE. MicroRNA regulation of lipid metabolism. Metabolism,2013,62:12-20
50. Freytag SO, Geddes TJ. Reciprocal regulation of adipogenesis by Myc and C/EBP alpha. Science,1992,256: 379-382
51. Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Research,2009,19:92-105
52. Fu M, Rao M, Bouras T, Wang C, Wu K, Zhang X, Li Z, Yao TP, Pestell RG Cyclin Dl inhibits peroxisome proliferator-activated receptor gamma-mediated adipogenesis through histone deacetylase recruitment. J Biol Chem,2005, 280: 16934-16941
53. Georges SA, Biery MC, Kim SY, Schelter JM, Guo J, Chang AN, Jackson AL, Carleton MO, Linsley PS, Cleary MA, Chau BN. Coordinated regulation of cell cycle transcripts by p53-Inducible microRNAs, miR-192 and miR-215. Cancer Res, 2008,68:10105-10112
54. Geraldo MV, Yamashita AS, Kimura ET. MicroRNA miR-146b-5p regulates signal transduction of TGF-beta by repressing SMAD4 in thyroid cancer. Oncogene,2012, 31:1910-1922
55. Gerin I, Bommer GT, McCoin CS, Sousa KM, Krishnan V, MacDougald OA. Roles for miRNA-378/378* in adipocyte gene expression and lipogenesis. Am J Physiol Endocrinol Metab,2010,299:E198-206
56. Gerin I, Clerbaux LA, Haumont O, Lanthier N, Das AK, Burant CF, Leclercq IA, MacDougald OA, Bommer GT. Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J Biol Chem, 2010, 285: 33652-33661
57. Gregoire FM, Smas CM, Sul HS. Understanding adipocyte differentiation. Physiol Rev, 1998,78:783-809
58. Guo Y, Chen Y, Zhang Y, Zhang Y, Chen L, Mo D. Up-regulated miR-145 expression inhibits porcine preadipocytes differentiation by targeting IRS1. Int J Biol Sci, 2012, 8:1408-1417
59. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW. Identification of c-MYC as a target of the APC pathway. Science,1998,281:1509-1512
60. Hilton C, Neville MJ, Karpe F. MicroRNAs in adipose tissue:their role in adipogenesis and obesity. Int J Obes (Lond),2013,37:325-332
61. Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene, 1989,77:51-59
62. Hoekstra M, van der Sluis RJ, Kuiper J, Van Berkel TJ. Nonalcoholic fatty liver disease is associated with an altered hepatocyte microRNA profile in LDL receptor knockout mice. J Nutr Biochem, 2012,23:622-628
63. Holmes A, Abraham DJ, Sa S, Shiwen X, Black CM, Leask A. CTGF and SMADs, maintenance of scleroderma phenotype is independent of SMAD signaling. J Biol Chem,2001,276:10594-10601
64. Huang J, Zhao L, Xing L, Chen D. MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells, 2010,28: 357-364
65. Huber LC, Stanczyk J, Jungel A, Gay S. Epigenetics in inflammatory rheumatic diseases. Arthritis Rheum,2007,56:3523-3531
66. Iliopoulos D, Drosatos K, Hiyama Y, Goldberg IJ, Zannis Ⅵ. MicroRNA-370 controls the expression of microRNA-122 and Cptlalpha and affects lipid metabolism. J Lipid Res,2010,51:1513-1523
67. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature,1990, 347:645-650
68. Jakobsson A, Westerberg R, Jacobsson A. Fatty acid elongases in mammals:their regulation and roles in metabolism. Prog Lipid Res,2006,45:237-249
69. Jia Z, Moulson CL, Pei Z, Miner JH, Watkins PA. Fatty acid transport protein 4 is the principal very long chain fatty acyl-CoA synthetase in skin fibroblasts. J Biol Chem,2007,282:20573-20583
70. Jing E, Gesta S, Kahn CR. SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. Cell Metab, 2007,6: 105-114
71. Karbiener M, Fischer C, Nowitsch S, Opriessnig P, Papak C, Ailhaud G, Dani C, Amri EZ, Scheideler M. microRNA miR-27b impairs human adipocyte differentiation and targets PPARgamma. Biochem Biophys Res Commun,2009,390: 247-251
72. Karbiener M, Neuhold C, Opriessnig P, Prokesch A, Bogner-Strauss JG, Scheideler M. MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1 and ALK2. RNA Biol,2011,8:850-860
73. Kennell JA, Gerin I, MacDougald OA, Cadigan KM. The microRNA miR-8 is a conserved negative regulator of Wnt signaling. Proc Natl Acad Sci U S A,2008,105: 15417-15422
74. Kennell JAG, I.;MacDougald, O. A.;Cadigan, K. M. The microRNA miR-8 is a conserved negative regulator of Wnt signaling. Proc Natl Acad Sci U S A, 2008,105: 15417-15422
75. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. Journal Of Clinical Endocrinology & Metabolism,2004,89:2548-2556
76. Killenberg PG, Davidson ED, Webster LT, Jr. Evidence for a medium-chain fatty acid: coenzyme A ligase (adenosine monophosphate) that activates salicylate. Mol Pharmacol,1971,7:260-268
77. Kim JB, Wright HM, Wright M, Spiegelman BM. ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand. Proc Natl Acad Sci U S A,1998,95:4333-4337
78. Kim SY, Kim AY, Lee HW, Son YH, Lee GY, Lee JW, Lee YS, Kim JB. miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression. Biochem Biophys Res Commun, 2010,392:323-328
79. Kim YJ, Hwang SH, Cho HH, Shin KK, Bae YC, Jung JS. MicroRNA 21 regulates the proliferation of human adipose tissue-derived mesenchymal stem cells and high-fat diet-induced obesity alters microRNA 21 expression in white adipose tissues. J Cell Physiol, 2012,227: 183-193
80. Kim YJ, Hwang SJ, Bae YC, Jung JS. MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue. Stem Cells,2009,27:3093-3102
81. Kinoshita M, Ono K, Horie T, Nagao K, Nishi H, Kuwabara Y, Takanabe-Mori R, Hasegawa K, Kita T, Kimura T. Regulation of adipocyte differentiation by activation of serotonin (5-HT) receptors 5-HT2AR and 5-HT2CR and involvement of microRNA-448-mediated repression of KLF5. Mol Endocrinol, 2010, 24:1978-1987
82. Kloosterman WP, Wienholds E, de Bruijn E, Kauppinen S, Plasterk RH. In situ detection of miRNAs in animal embryos using LNA-modified oligonucleotide probes. Nat Methods,2006,3:27-29
83. Kobayashi T, Zadravec D, Jacobsson A. ELOVL2 overexpression enhances triacylglycerol synthesis in 3T3-L1 and F442A cells. FEBS Lett, 2007, 581: 3157-3163
84. Konig B, Koch A, Spielmann J, Hilgenfeld C, Stangl GI, Eder K. Activation of PPARalpha lowers synthesis and concentration of cholesterol by reduction of nuclear SREBP-2. Biochem Pharmacol,2007,73:574-585
85. Koolman J, Rohm KH. Color atlas of biochemistry. Thieme; 2005.
86. Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N. Combinatorial microRNA target predictions. Nat Genet,2005,37:495-500
87. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol,2002,12: 735-739
88. Laiho M, DeCaprio JA, Ludlow JW, Livingston DM, Massague J. Growth inhibition by TGF-beta linked to suppression of retinoblastoma protein phosphorylation. Cell, 1990,62:175-185
89. Landschulz WH, Johnson PF, Adashi EY, Graves BJ, McKnight SL. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev, 1988,2:786-800
90. Leask A, Holmes A, Black CM, Abraham DJ. Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in fibroblasts. J Biol Chem,2003,278:13008-13015
91. Lee EK, Lee MJ, Abdelmohsen K, Kim W, Kim MM, Srikantan S, Martindale JL, Hutchison ER, Kim HH, Marasa BS, Selimyan R, Egan JM, Smith SR, Fried SK, Gorospe M. miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression. Mol Cell Biol, 2011,31:626-638
92. Lee JC, Zhao JT, Clifton-Bligh RJ, Gill A, Gundara JS, Ip JC, Glover A, Sywak MS, Delbridge LW, Robinson BG, Sidhu SB. MicroRNA-222 and MicroRNA-146b Are Tissue and Circulating Biomarkers of Recurrent Papillary Thyroid Cancer. Cancer, 2013,119:4358-4365
93. Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science,2001,294:862-864
94. Lee RC, Gowrishankar TR, Basch RM, Patel PK, Golan DE. Cell shape-dependent rectification of surface receptor transport in a sinusoidal electric field. Biophys J, 1993,64:44-57
95. Lee SL, Sadovsky Y, Swirnoff AH, Polish JA, Goda P, Gavrilina G, Milbrandt J. Luteinizing hormone deficiency and female infertility in mice lacking the transcription factor NGFI-A(Egr-l). Science, 1996,273:1219-1221
96. Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J,2002,21:4663-4670
97. Lefterova MI, Lazar MA. New developments in adipogenesis. Trends Endocrinol Metab,2009,20:107-114
98. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 2005,120:15-20
99. Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell,2003,115:787-798
100. Li MO, Flavell RA. TGF-beta: a master of all T cell trades. Cell, 2008,134:392-404
101. Li S, Gao J, Gu J, Yuan J, Hua D, Shen L. MicroRNA-215 inhibits relapse of colorectal cancer patients following radical surgery. Medical Oncology, 2013,30:
102. Liao WT, Li TT, Wang ZG, Wang SY, He MR, Ye YP, Qi L, Cui YM, Wu P, Jiao HL, Zhang C, Xie YJ, Wang JX, Ding YQ. microRNA-224 promotes cell proliferation and tumor growth in human colorectal cancer by repressing PHLPP1 and PHLPP2. Clin Cancer Res,2013,19:4662-4672
103. Lin FT, Lane MD. CCAAT/enhancer binding protein alpha is sufficient to initiate the 3T3-L1 adipocyte differentiation program. Proc Natl Acad Sci U S A, 1994, 91: 8757-8761
104. Lin Q, Gao Z, Alarcon RM, Ye J, Yun Z. A role of miR-27 in the regulation of adipogenesis. FEBS J, 2009,276:2348-2358
105. Ling HY, Wen GB, Feng SD, Tuo QH, Ou HS, Yao CH, Zhu BY, Gao ZP, Zhang L, Liao DF. MicroRNA-375 promotes 3T3-L1 adipocyte differentiation through modulation of extracellular signal-regulated kinase signalling. Clin Exp Pharmacol Physiol, 2011,38:239-246
106. Linhart HG, Ishimura-Oka K, DeMayo F, Kibe T, Repka D, Poindexter B, Bick RJ, Darlington GJ. C/EBPalpha is required for differentiation of white, but not brown, adipose tissue. Proc Natl Acad Sci U S A, 2001,98:12532-12537
107. Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M, Dumitru CD, Shimizu M, Zupo S, Dono M, Alder H, Bullrich F, Negrini M, Croce CM. An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci U S A, 2004,101:9740-9744
108. Liu S, Yang Y, Wu J. TNFalpha-induced up-regulation of miR-155 inhibits adipogenesis by down-regulating early adipogenic transcription factors. Biochem Biophys Res Commun, 2011,414:618-624
109. Lonn P, Moren A, Raja E, Dahl M, Moustakas A. Regulating the stability of TGFbeta receptors and Smads. Cell Res, 2009, 19:21-35
110. Lowe CE, O'Rahilly S, Rochford JJ. Adipogenesis at a glance. Journal Of Cell Science,2011,124:2681-2686
111. Lowe CE, O'Rahilly S, Rochford JJ. Adipogenesis at a glance. J Cell Sci, 2011,124: 2681-2686
112. Lu J, Fu Y, Kumar S, Shen Y, Zeng K, Xu A, Carthew R, Wu CI. Adaptive evolution of newly emerged micro-RNA genes in Drosophila. Mol Biol Evol, 2008,25: 929-938
113. Luquet S, Gaudel C, Holst D, Lopez-Soriano J, Jehl-Pietri C, Fredenrich A, Grimaldi PA. Roles of PPAR delta in lipid absorption and metabolism: a new target for the treatment of type 2 diabetes. Biochim Biophys Acta, 2005, 1740: 313-317
114. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling:components, mechanisms, and diseases. Dev Cell,2009,17:9-26
115. MacDougald OA, Lane MD. Transcriptional regulation of gene expression during adipocyte differentiation. Annu Rev Biochem, 1995,64:345-373
116. Mann B, Gelos M, Siedow A, Hanski ML, Gratchev A, Ilyas M, Bodmer WF, Moyer MP, Riecken EO, Buhr HJ, Hanski C. Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci U S A,1999,96:1603-1608
117. Marquart TJ, Allen RM, Ory DS, Baldan A. miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci U S A, 2010,107:12228-12232
118. Martinelli R, Nardelli C, Pilone V, Buonomo T, Liguori R, Castano I, Buono P, Masone S, Persico G, Forestieri P, Pastore L, Sacchetti L. miR-519d overexpression is associated with human obesity. Obesity (Silver Spring), 2010, 18:2170-2176
119. Mashek DG, Bornfeldt KE, Coleman RA, Berger J, Bernlohr DA, Black P, DiRusso CC, Farber SA, Guo W, Hashimoto N, Khodiyar V, Kuypers FA, Maltais LJ, Nebert DW, Renieri A, Schaffer JE, Stahl A, Watkins PA, Vasiliou V, Yamamoto TT. Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family. J Lipid Res, 2004,45:1958-1961
120. Massague J, Blain SW, Lo RS. TGFbeta signaling in growth control, cancer, and heritable disorders. Cell, 2000,103:295-309
121.Mees ST, Mardin WA, Sielker S, Willscher E, Senninger N, Schleicher C, Colombo-Benkmann M, Haier J. Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas. Ann Surg Oncol, 2009,16:2339-2350
122. Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B, Rigoutsos I. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell, 2006,126:1203-1217
123. Miyanari Y, Torres-Padilla ME. Epigenetic regulation of reprogramming factors towards pluripotency in mouse preimplantation development. Curr Opin Endocrinol Diabetes Obes,2010,17:500-506
124. Moon YA, Shah NA, Mohapatra S, Warrington JA, Horton JD. Identification of a mammalian long chain fatty acyl elongase regulated by sterol regulatory element-binding proteins. J Biol Chem, 2001,276:45358-45366
125. Mori T, Sakaue H, Iguchi H, Gomi H, Okada Y, Takashima Y, Nakamura K, Nakamura T, Yamauchi T, Kubota N, Kadowaki T, Matsuki Y, Ogawa W, Hiramatsu R, Kasuga M. Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J Biol Chem, 2005,280:12867-12875
126. Mulligan C, Rochford J, Denyer G, Stephens R, Yeo G, Freeman T, Siddle K, O'Rahilly S. Microarray analysis of insulin and insulin-like growth factor-1 (IGF-1) receptor signaling reveals the selective up-regulation of the mitogen heparin-binding EGF-like growth factor by IGF-1. J Biol Chem, 2002,277:42480-42487
127. Nagel R, le Sage C, Diosdado B, van der Waal M, Oude Vrielink JA, Bolijn A, Meijer GA, Agami R. Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer. Cancer Res, 2008,68:5795-5802
128. Najafi-Shoushtari SH, Kristo F, Li Y, Shioda T, Cohen DE, Gerszten RE, Naar AM. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science,2010,328:1566-1569
129. Nakachi Y, Yagi K, Nikaido I, Bono H, Tonouchi M, Schonbach C, Okazaki Y. Identification of novel PPARgamma target genes by integrated analysis of ChlP-on-chip and microarray expression data during adipocyte differentiation. Biochem Biophys Res Commun, 2008,372:362-366
130. Nakanishi N, Nakagawa Y, Tokushige N, Aoki N, Matsuzaka T, Ishii K, Yahagi N, Kobayashi K, Yatoh S, Takahashi A, Suzuki H, Urayama O, Yamada N, Shimano H. The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice. Biochem Biophys Res Commun, 2009,385:492-496
131.Navarro A, Diaz T, Martinez A, Gaya A, Pons A, Gel B, Codony C, Ferrer G, Martinez C, Montserrat E, Monzo M. Regulation of JAK2 by miR-135a:prognostic impact in classic Hodgkin lymphoma. Blood,2009,114:2945-2951
132. Ntambi JM, Young-Cheul K. Adipocyte differentiation and gene expression. J Nutr, 2000,130:3122S-3126S
133. Oishi Y, Manabe I, Tobe K, Tsushima K, Shindo T, Fujiu K, Nishimura G, Maemura K, Yamauchi T, Kubota N, Suzuki R, Kitamura T, Akira S, Kadowaki T, Nagai R. Kruppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation. Cell Metab,2005,1:27-39
134. Oller do Nascimento CM, Ribeiro EB, Oyama LM. Metabolism and secretory function of white adipose tissue:effect of dietary fat. An Acad Bras Cienc, 2009,81: 453-466
135. Ospelt C, Reedquist KA, Gay S, Tak PP. Inflammatory memories:is epigenetics the missing link to persistent stromal cell activation in rheumatoid arthritis? Autoimmun Rev, 2011,10:519-524
136. Otto TC, Lane MD. Adipose development:from stem cell to adipocyte. Crit Rev Biochem Mol Biol,2005,40:229-242
137. Ou Z, Wada T, Gramignoli R, Li S, Strom SC, Huang M, Xie W. MicroRNA hsa-miR-613 targets the human LXRalpha gene and mediates a feedback loop of LXRalpha autoregulation. Mol Endocrinol,2011,25:584-596
138. Pang RTK, Liu W-M, Leung CON, Ye T-M, Kwan PCK, Lee K-F, Yeung WSB. miR-135A Regulates Preimplantation Embryo Development through Down-Regulation of E3 Ubiquitin Ligase Seven in Absentia Homolog 1A(SIAH1A) Expression. Plos One, 2011,6:
139. Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Muller P, Spring J, Srinivasan A, Fishman M, Finnerty J, Corbo J, Levine M, Leahy P, Davidson E, Ruvkun G. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature, 2000,408:86-89
140. Patnaik SK, Kannisto E, Mallick R, Yendamuri S. Overexpression of the lung cancer-prognostic miR-146b microRNAs has a minimal and negative effect on the malignant phenotype of A549 lung cancer cells. PLoS One, 2011,6:e22379
141. Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L. Sirtl promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature, 2004,429:771-776
142. Prestwich TC, Macdougald OA. Wnt/beta-catenin signaling in adipogenesis and metabolism. Curr Opin Cell Biol, 2007,19:612-617
143. Qin L, Chen Y, Niu Y, Chen W, Wang Q, Xiao S, Li A, Xie Y, Li J, Zhao X, He Z, Mo D. A deep investigation into the adipogenesis mechanism: profile of microRNAs regulating adipogenesis by modulating the canonical Wnt/beta-catenin signaling pathway. BMC Genomics,2010,11:320
144. Rahimi N, Tremblay E, McAdam L, Roberts A, Elliott B. Autocrine secretion of TGF-beta 1 and TGF-beta 2 by pre-adipocytes and adipocytes:a potent negative regulator of adipocyte differentiation and proliferation of mammary carcinoma cells. In Vitro Cell Dev Biol Anim, 1998,34:412-420
145. Rakyan V, Whitelaw E. Transgenerational epigenetic inheritance. Curr Biol, 2003, 13:R6
146. Ramirez CM, Davalos A, Goedeke L, Salerno AG, Warrier N, Cirera-Salinas D, Suarez Y, Fernandez-Hernando C. MicroRNA-758 regulates cholesterol efflux through posttranscriptional repression of ATP-binding cassette transporter Al. Arterioscler Thromb Vase Biol,2011,31:2707-2714
147. Ramji DP, Foka P. CCAAT/enhancer-binding proteins:structure, function and regulation. Biochem J, 2002,365:561-575
148. Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE, Parathath S, van Gils JM, Rayner AJ, Chang AN, Suarez Y, Fernandez-Hernando C, Fisher EA, Moore KJ. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J Clin Invest,2011,121:2921-2931
149. Rayner KJ, Suarez Y, Davalos A, Parathath S, Fitzgerald ML, Tamehiro N, Fisher EA, Moore KJ, Fernandez-Hernando C. MiR-33 contributes to the regulation of cholesterol homeostasis. Science,2010,328:1570-1573
150. Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R. Fast and effective prediction of microRNA/target duplexes. RNA,2004, 10: 1507-1517
151. Richardson RL, Campion DR, Hausman GJ, Wright JT. Transforming growth factor type beta (TGF-beta) and adipogenesis in pigs. Journal of animal science, 1989,67: 2171-2180
152. Rochford JJ, Semple RK, Laudes M, Boyle KB, Christodoulides C, Mulligan C, Lelliott CJ, Schinner S, Hadaschik D, Mahadevan M, Sethi JK, Vidal-Puig A, O'Rahilly S. ETO/MTG8 is an inhibitor of C/EBPbeta activity and a regulator of early adipogenesis. Mol Cell Biol,2004,24:9863-9872
153. Rodriguez-Rodero S, Fernandez-Morera JL, Fernandez AF, Menendez-Torre E, Fraga MF. Epigenetic regulation of aging. Discovery medicine, 2010, 10:225-233
154. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian micro RNA host genes and transcription units. Genome Res, 2004, 14: 1902-1910
155. Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ, Spiegelman BM. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes Dev,2002,16:22-26
156. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev,2000,14:1293-1307
157. Ross S, Hill CS. How the Smads regulate transcription. International Journal Of Biochemistry & Cell Biology, 2008,40:383-408
158. Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL, MacDougald OA. Inhibition of adipogenesis by Wnt signaling. Science,2000,289:950-953
159. Ruvkun G. Molecular biology. Glimpses of a tiny RNA world. Science, 2001,294: 797-799
160. Salma N, Xiao H, Imbalzano AN. Temporal recruitment of CCAAT/enhancer-binding proteins to early and late adipogenic promoters in vivo. J Mol Endocrinol,2006,36:139-151
161. Schmierer B, Hill CS. TGFbeta-SMAD signal transduction:molecular specificity and functional flexibility. Nat Rev Mol Cell Biol, 2007,8: 970-982
162. Schneider-Maunoury S, Topilko P, Seitandou T, Levi G, Cohen-Tannoudji M, Pournin S, Babinet C, Charnay P. Disruption of Krox-20 results in alteration of rhombomeres 3 and 5 in the developing hindbrain. Cell,1993,75:1199-1214
163. Scisciani C, Vossio S, Guerrieri F, Schinzari V, De Iaco R, D'Onorio de Meo P, Cervello M, Montalto G, Pollicino T, Raimondo G, Levrero M, Pediconi N. Transcriptional regulation of miR-224 upregulated in human HCCs by NFkappaB inflammatory pathways. J Hepatol, 2012,56:855-861
164.Shi R, Sun YH, Zhang XH, Chiang VL. Poly(T) adaptor RT-PCR. Methods Mol Biol, 2012,822:53-66
165. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell, 2003,113:685-700
166. Shi Y, Wang YF, Jayaraman L, Yang H, Massague J, Pavletich NP. Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling. Cell,1998,94:585-594
167. Shtutman M, Zhurinsky J, Simcha I, Albanese C, D'Amico M, Pestell R, Ben-Ze'ev A. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad SciU S A,1999,96: 5522-5527
168. Shulman AI, Mangelsdorf DJ. Retinoid x receptor heterodimers in the metabolic syndrome. N Engl J Med, 2005,353:604-615
169. Song B, Wang Y, Titmus MA, Botchkina G, Formentini A, Kornmann M, Ju J. Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells. Mol Cancer,2010,9:96
170. Soupene E, Kuypers FA. Mammalian long-chain acyl-CoA synthetases. Exp Biol Med (Maywood),2008,233:507-521
171. Sparks RL, Allen BJ, Strauss EE. TGF-beta blocks early but not late differentiation-specific gene expression and morphologic differentiation of 3T3 T proadipocytes. J Cell Physiol, 1992,150:568-577
172. Sun T, Fu M, Bookout AL, Kliewer SA, Mangelsdorf DJ. MicroRNA let-7 regulates 3T3-L1 adipogenesis. Mol Endocrinol,2009,23:925-931
173. Swiatek PJ, Gridley T. Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20. Genes Dev, 1993,7:2071-2084
174. Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of micro RNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A,2006, 103:12481-12486
175. Tago K, Nakamura T, Nishita M, Hyodo J, Nagai S, Murata Y, Adachi S, Ohwada S, Morishita Y, Shibuya H, Akiyama T. Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein. Genes Dev,2000,14:1741-1749
176. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res,2004,64:3753-3756
177.Takanabe R, Ono K, Abe Y, Takaya T, Horie T, Wada H, Kita T, Satoh N, Shimatsu A, Hasegawa K. Up-regulated expression of micro RNA-143 in association with obesity in adipose tissue of mice fed high-fat diet. Biochem Biophys Res Commun, 2008, 376:728-732
178. Tan JT, McLennan SV, Song WW, Lo LW, Bonner JG, Williams PF, Twigg SM. Connective tissue growth factor inhibits adipocyte differentiation. Am J Physiol Cell Physiol,2008,295:C740-751
179. Tanaka T, Yoshida N, Kishimoto T, Akira S. Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene. EMBO J,1997,16:7432-7443
180. Tang W-w, Wan G-p, Wan Y-c, Zhang L, Cheng W-j. Effects of miR-135a on HOXA10 expression, proliferation and apoptosis of ovarian cancer cells. Zhonghua fu chan ke za zhi, 2013,48:364-369
181. Taylor AW. Review of the activation of TGF-beta in immunity. J Leukoc Biol, 2009, 85:29-33
182. Teleman AA, Maitra S, Cohen SM. Drosophila lacking microRNA miR-278 are defective in energy homeostasis. Genes Dev,2006,20:417-422
183. Teran-Garcia M, Bouchard C. Genetics of the metabolic syndrome. Appl Physiol Nutr Metab,2007,32:89-114
184. Tetsu O, McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature,1999,398:422-426
185. Tominaga K, Kondo C, Johmura Y, Nishizuka M, Imagawa M. The novel gene fad104, containing a fibronectin type III domain, has a significant role in adipogenesis. FEBS Lett,2004,577:49-54
186. Tong Q, Tsai J, Tan G, Dalgin G, Hotamisligil GS. Interaction between GATA and the C/EBP family of transcription factors is critical in GATA-mediated suppression of adipocyte differentiation. Mol Cell Biol,2005,25:706-715
187. Tontonoz P, Spiegelman BM. Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem,2008,77:289-312
188. Topilko P, Schneider-Maunoury S, Levi G, Baron-Van Evercooren A, Chennoufi AB, Seitanidou T, Babinet C, Charnay P. Krox-20 controls myelination in the peripheral nervous system. Nature, 1994,371:796-799
189. Torti FM, Torti SV, Larrick JW, Ringold GM. Modulation of adipocyte differentiation by tumor necrosis factor and transforming growth factor beta. J Cell Biol,1989,108:1105-1113
190. Tourtellotte WG, Milbrandt J. Sensory ataxia and muscle spindle agenesis in mice lacking the transcription factor Egr3. Nat Genet,1998,20:87-91
191. Waddington CH. The epigenotype. 1942. Int J Epidemiol,2012,41:10-13
192. Wang Q, Li YC, Wang J, Kong J, Qi Y, Quigg RJ, Li X. miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/pl30. Proc Natl Acad Sci U S A, 2008,105:2889-2894
193. Wang Y, Lee AT, Ma JZ, Wang J, Ren J, Yang Y, Tantoso E, Li KB, Ooi LL, Tan P, Lee CG Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regulation and apoptosis inhibitor-5 as a microRNA-224-specific target. J Biol Chem, 2008,283:13205-13215
194. Whitman M. Smads and early developmental signaling by the TGFbeta superfamily. Genes Dev,1998,12:2445-2462
195. Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E, Horvitz HR, Kauppinen S, Plasterk RH. MicroRNA expression in zebrafish embryonic development. Science, 2005,309:310-311
196. Williams AH, Liu N, van Rooij E, Olson EN. MicroRNA control of muscle development and disease. Curr Opin Cell Biol, 2009,21:461-469
197. Wu Z, Bucher NL, Farmer SR. Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids. Mol Cell Biol, 1996,16: 4128-4136
198. Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, McKeon C, Darlington GJ, Spiegelman BM. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell, 1999,3: 151-158
199. Wu Z, Xie Y, Bucher NL, Farmer SR. Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. Genes Dev, 1995,9:2350-2363
200. Xia H, Qi Y, Ng SS, Chen X, Li D, Chen S, Ge R, Jiang S, Li G, Chen Y, He ML, Kung HF, Lai L, Lin MC. microRNA-146b inhibits glioma cell migration and invasion by targeting MMPs. Brain Res,2009,1269:158-165
201. Xie H, Lim B, Lodish HF. MicroRNAs Induced During Adipogenesis that Accelerate Fat Cell Development Are Downregulated in Obesity. Diabetes, 2009, 58:1050-1057
202. Xu P-F, Houssin N, Ferri-Lagneau KF, Thisse B, Thisse C. Construction of a Vertebrate Embryo from Two Opposing Morphogen Gradients. Science,2014,344: 87-89
203. Xu P, Vernooy SY, Guo M, Hay BA. The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol, 2003,13:790-795
204. Xu PV, S. Y.;Guo, M.;Hay, B. A. The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol, 2003,13:790-795
205. Yang Z, Bian C, Zhou H, Huang S, Wang S, Liao L, Zhao RC. MicroRNA hsa-miR-138 inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells through adenovirus EID-1. Stem Cells Dev, 2011,20: 259-267
206. Yang Z, Ebright YW, Yu B, Chen X. HEN1 recognizes 21-24 nt small RNA duplexes and deposits a methyl group onto the 2' OH of the 3'terminal nucleotide. Nucleic Acids Res,2006,34:667-675
207. Zaragosi LE, Wdziekonski B, Brigand KL, Villageois P, Mari B, Waldmann R, Dani C, Barbry P. Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis. Genome Biol,2011,12:R64
208.Zhang L, Hou D, Chen X, Li D, Zhu L, Zhang Y, Li J, Bian Z, Liang X, Cai X, Yin Y, Wang C, Zhang T, Zhu D, Zhang D, Xu J, Chen Q, Ba Y, Liu J, Wang Q et al. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res,2012,22:107-126
209. Zheng L, Lv GC, Sheng J, Yang YD. Effect of miRNA-l0b in regulating cellular steatosis level by targeting PPAR-alpha expression, a novel mechanism for the pathogenesis of NAFLD. J Gastroenterol Hepatol,2010,25:156-163
210. Zizola CF, Frey SK, Jitngarmkusol S, Kadereit B, Yan N, Vogel S. Cellular retinol-binding protein type I (CRBP-I) regulates adipogenesis. Mol Cell Biol,2010, 30:3412-3420
211.Zuo Y, Qiang L, Farmer SR. Activation of CCAAT/enhancer-binding protein (C/EBP) alpha expression by C/EBP beta during adipogenesis requires a peroxisome proliferator-activated receptor-gamma-associated repression of HDAC1 at the C/ebp alpha gene promoter. J Biol Chem, 2006,281:7960-7967