UVB相关的miRNAs的筛选及其功能的初步研究
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摘要
近年来,一类叫做microRNAs(miRNAs)的非编码小RNA分子,在监控个体发育时相转变、调控特定细胞增殖、分化进程等方面起着重要作用。其在紫外线的致损伤和致病机制中的作用,逐渐被科学家们发现。通过高通量筛选miRNAs的技术平台获得UVB相关的miRNAs,是研究UVB敏感miRNAs的起点。因此,本课题采用miRNAs基因芯片筛选UVB相关miRNAs,生物信息学分析及验证其作用靶点,并探讨其在表皮癌中的作用,研究结果为探明miRNAs调控造紫外线的致损伤的分子机制、探索miRNA在表皮癌中作用提供理论指导和实验依据。
研究目的：应用miRNAs芯片筛选UVB照射的NIH3T3细胞表达miRNAs,并寻找差异表达miRNAs调控的靶基因,为进一步研究miRNAs在UVB诱导的信号传导通路中的作用打下基础；对hsa-miR-365生物学预测的靶基因NFIB/BCL2/CDK6进行实验验证,先从结构学方面来验证miRNA/mRNA的相互作用,为从功能学方面研究它们之间的关系做好了准备；研究皮肤癌A431中hsa-miR-365的表达,并探讨hsa-miR-365的抑制片段对体外生长的人皮肤癌细胞A431的抑制作用,确立miR-365与表皮癌之间的联系,为进一步研究miR-365在表皮中的作用指出新的方向。
方法：MTT法、流式细胞术和AO/EB染色检测细胞的形态学改变；运用miRNAs芯片技术筛选UVB照射的NIH3T3细胞差异表达miRNAs,同时运用miRNAs特异的引物组对差异表达的miRNAs进行荧光定量RT-PCR验证。运用靶基因预测软件预测差异表达miRNAs可能调控的靶基因,并利用DAVID Bioinformatics Resources 2008数据库将预测的靶基因进行了分析。
利用在线数据库TargetScan等预测miR-365的靶基因,在A431细胞中,Lipofectamine2000转染hsa-miR-365 inhibitor后,用real-time qPCR、western blot分别从RNA水平和蛋白水平检测BCL2、CDK6和NFIB的表达,并用psi-CHECK2荧光表达报告载体验证NFIB为miR-365的直接靶基因。
采用荧光定量RT-PCR的方法鉴定了hsa-miR-365在皮肤鳞癌A431中的表达特性,用Lipofectamine2000转染皮肤鳞癌细胞株后,进一步采用Transwell小室检测miR-365抑制后细胞体外运动能力的改变,采用Boyden小室检测miR-365抑制后细胞体外侵袭能力的改变,平板克隆形成实验和流式细胞术检测细胞增殖和凋亡。
结果：MTT结果,NIH3T3细胞在受到不同剂量的UVB照射后,50J／m2的UVB其生存率为60%左右,再继续加大UVB的剂量,其生存率明显下降,故50J／m2的UVB是我们实验所选取的合适剂量。NIH3T3接受50J／m2后,继续培养不同的时间点,发现NIH3T3细胞在照射后的2h,4h,6h和12h其生存率变化显著,故我们选择这些时间点进行后面的miRNAs芯片分析。流式细胞仪分析显示：NIH3T3细胞在50J/m2 UVB照射后的12h,G1期细胞群的比例明显提高,而且出现了一个明显的凋亡峰和G1期细胞阻滞。NIH3T3细胞经50J/m2 UVB照射后继续培养12h,可见早期凋亡细胞,表现为细胞核为AO染色呈黄绿色荧光,浓聚成颗粒状；在细胞的一侧,可见细胞出芽。
miRNAs芯片结果显示,实验组细胞与对照组细胞差异表达的miRNA共30个(占11%),其中27个表达上调,3个表达下调。有趣的是,mmu-miR-365和mmu-miR-21显著上调,而mmu-miR-465在不同的时间点都下调。其差异表达均在2倍以上；Mmu-miR-let-7a, mmu-miR-24, mmu-miR-376b和mmu-miR-21的实时荧光定量RT-PCR验证结果与芯片表达结果基本一致。信号通路分析发现,miR-24参与MAPK等信号通路,miR-21参与Jak-STAT等信号通路。
利用TargetScan等多个靶基因的预测软件对miR-365的靶基因进行预测,结合GO分析,最后我们确定对NFIB、BCL2和CDK6这三个靶基因进行实验验证。在miR-365表达量较高的A431细胞中转染hsa-miR-365 inhibitor后,发现三个靶基因在RNA水平没有改变,而其蛋白水平,较对照组升高。这些结果说明,hsa-miR-365是在靶基因的蛋白水平发挥作用,而不影响靶基因的转录。将NFIB基因的3’UTR区克隆在荧光素酶报告载体psiCHECK-2的报告基因的下游,用Lipofectamine2000转染至A431细胞,DualLuciferaseTM检测荧光蛋白酶的活性,结果显示,相对于对照组,转染hsa-miR-365组的荧光素酶的表达量具有显著差异。这提示了miR-365是通过其NFIB的3’UTR发挥作用,且NFIB是其直接的靶基因。
Hsa-miR-365在皮肤鳞癌A431中表达是正常角质形成细胞的15倍,平板克隆形成实验结果显示,与空白对照组和错义转染组比较,hsa-miR-365反义片段转染的细胞增殖速度明显减慢(p<0.001),流式细胞仪结果显示三组的细胞周期分布没有明显差异(p>0.05)。Transwell小室结果显示,反义片段组细胞穿过聚碳酸酯膜的细胞数减少,差异具有显著性(p<0.001)。Boyden小室结果显示,反义片段组细胞细胞的侵袭能力显著降低(p<0.001)。
结论：我们的研究揭示了UVB辐射和miRNAs的联系,寻找出了在特定条件下对UVB敏感的miRNAs,这为研究受UVB调节的miRNA表达提供了基本的依据。我们进一步证明了NFIB是miR-365的靶基因,miR-365在蛋白水平抑制NFIB的表达,而不影响其转录,它们之间是通过NFIB 3'UTR相互作用的。hsa-miR-365在表皮癌细胞A431中高表达,将其抑制后显著降低了皮肤鳞癌细胞的体外迁移和侵袭能力,为研究miR-365在皮肤癌中的功能打了一定的基础。
Rencently, a class of non-coding RNAs called microRNAs (miRNAs), play an an important role in monitoring development phase changes of individual, in regulation of specific cell proliferation, differentiation and other aspects of the process. The role of miRNAs in UVB induced damages and diseases are gradually discovered by scientists.UVB relative miRNAs are found by miRNAs array, which is a start for studying UVB sensentive miRNAs. Therefore, targets genes of miRNAs were verified by bioinformatics and experiments. Furthermore, we analysed the role of miRNAs in epidermal carcinoma.The results provide the theory and experiment basis for the study of the UV-induced damage in the molecular mechanism and the role of miRNA in epidermal carcinoma.
Aim:To investigate the differentially expressed miRNAs and their target genes in NIH3T3 cells after UVB irradiation, which are useful for further studies on functions of miRNAs in UVB induced signal transduction pathway. Furthermore, to comfirm the target genes of hsa-miR-365 from structure, preparing for the study on function, to study the expression level of hsa-miR-365 in epidermal carcinoma and investigate the role of hsa-miR-365 inhibitor in A431 cells in vitro, which established the relationship between miR-365 and epidermal carcinoma and pointed out a new direction for studying epidermal carcinoma.
Methods:MTT, Flow Cytometry and AO/EB staining were used to detect cell morphological changes in NIH3T3. MicroRNA microarray was used to examine the differentially expressed miRNAs in NIH3T3 cells after UVB irradiation, and the discovered miRNAs were confirmed by real time RT-PCR assay. Targets predictions were performed by Microcosm and TargetScan and Potential target genes of these miRNAs were classified into different function categories with the GOstat software (http://gostat.wehi.edu.au/cgi-bin/goStat.pl).
Hsa-miR-365 target genes were predicted by availble data TargetScan. After hsa-miR-365 inhibitor were transfected A431 cells by Lipofectamine2000, Real-time qPCR, western blot were used to test the expression level at RNA and protein level. And Luciferase activty assay were performed to confirm the targets of hsa-miR-365 after hsa-miR-365 tansferred A431 cells.
Hsa-miR-365 expression level was test by real time RT-PCR assay in A431 cells. Corning Transwell Inserts and Boyden chamber were used to test the migration and invasion of A431 cells respectively. Meanwhile, pate clone forming assay and flow cytometry were used to examed the cell proliferation and apoptosis.
Results:the results of MTT showed that there was a great change in 50J/m2 UVB dose; when NIH3T3 cells were continued to culture 2h,4h,6h and 12h after 50J/m2 UVB irradiation, the change of survival rate was rapid in these piont. Morever, the results of flow cytometry showed there was an G1 arrest and an apoptosis peak at 12h after 50J/m2 UVB irradiation. AO/EB straining showed that typital apoptosis at 12h after 50J/m2 UVB irradiation. In some cells stained with EB, the nuclei exhibit bright condensed chromatin or fragmented chromatin, some cells showed apoptotic bleb phenomenon.
MicroRNA microarray showed that 30 miRNAs were differentially expressed, accounting for 11%, in which 27 up-regulated,3 down-regulated. Interestingly, the express level of mmu-miR-365 and mmu-miR-21 were more than six times, while mmu-miR-465 showed low levels of expression at all time points. The expression levels of mmu-miR-let-7a, mmu-miR-24, mmu-miR-376b and mmu-miR-21 were accordant with the results from real time RT-PCR. Single pathway analysis showed that miR-24 involed in MAPK signaling pathway, miR-21 involved in Jak-STAT signaling pathway.
To predict the target genes of miR-365 using TargetScan and other softwares, combined with GO analysis, we decided to confirmed the targets genes NFIB、BCL2 and CDK6 by experiment methods. After hsa-miR-365 inhibitors were transfected to A431 cells, we found that there was no change in the three target genes at RNA level, but their protein level increased compared with the control and negative control. Luciferase activty assay showed that there was a significant difference in the luciferase activty assay with miR-365 inhibitors among the three groups (p<0.05).
The expression level of hsa-miR-365 in A431 cells is more than 15 times as high as control.The results of vitro invasion assay showed that A431 cells with hsa-miR-356 inhibitors had significantly reduced in invasiveness as compared with control and negative control(F=111.709, P＜0.001). Furthermore, A431 cells with hsa-miR-356 inhibitor also caused a significant decrease of motility compared with control and negative control by use of Corning Transwell Inserts(F=41.732, P<0.001). All of these results showed low expression of miR-365 partially led to a downregulated migration and invasion of A431 cells. In addition, the ability to form colonies in plate of A431 cells with hsa-miR-365 inhibitors was significant reduced compareing that in control and negative control (F=30.077, P<0.001). However, the cell cycle distribution detected by flow cytometry is not significantly different among each other. These results revealed lower expression of miR-365 partially suppress proliferatin of A431 cells (P> 0.05).
Conclusions:Our research reveals the radiation between UVB radiation and miRNAs. We found the UVB sensentive miRNAs, which provides a basis for studying the regulation of miRNA expression in UVB radiation. Furthermore, we confirmed that NFIB is a direct target of miR-365, repressing the NFIB protein expression, not NFIB RNA. Hsa-miR-365 highly expressed in epidermal cancer cells A431 and hsa-miR-365 inhibitors significantly reduce skin cancer cell migration and invasion in vitro, laying a foundation for studying the function of skin cancer.
研究目的：应用miRNAs芯片筛选UVB照射的NIH3T3细胞表达miRNAs,并寻找差异表达miRNAs调控的靶基因,为进一步研究miRNAs在UVB诱导的信号传导通路中的作用打下基础；对hsa-miR-365生物学预测的靶基因NFIB/BCL2/CDK6进行实验验证,先从结构学方面来验证miRNA/mRNA的相互作用,为从功能学方面研究它们之间的关系做好了准备；研究皮肤癌A431中hsa-miR-365的表达,并探讨hsa-miR-365的抑制片段对体外生长的人皮肤癌细胞A431的抑制作用,确立miR-365与表皮癌之间的联系,为进一步研究miR-365在表皮中的作用指出新的方向。
方法：MTT法、流式细胞术和AO/EB染色检测细胞的形态学改变；运用miRNAs芯片技术筛选UVB照射的NIH3T3细胞差异表达miRNAs,同时运用miRNAs特异的引物组对差异表达的miRNAs进行荧光定量RT-PCR验证。运用靶基因预测软件预测差异表达miRNAs可能调控的靶基因,并利用DAVID Bioinformatics Resources 2008数据库将预测的靶基因进行了分析。
利用在线数据库TargetScan等预测miR-365的靶基因,在A431细胞中,Lipofectamine2000转染hsa-miR-365 inhibitor后,用real-time qPCR、western blot分别从RNA水平和蛋白水平检测BCL2、CDK6和NFIB的表达,并用psi-CHECK2荧光表达报告载体验证NFIB为miR-365的直接靶基因。
采用荧光定量RT-PCR的方法鉴定了hsa-miR-365在皮肤鳞癌A431中的表达特性,用Lipofectamine2000转染皮肤鳞癌细胞株后,进一步采用Transwell小室检测miR-365抑制后细胞体外运动能力的改变,采用Boyden小室检测miR-365抑制后细胞体外侵袭能力的改变,平板克隆形成实验和流式细胞术检测细胞增殖和凋亡。
结果：MTT结果,NIH3T3细胞在受到不同剂量的UVB照射后,50J／m2的UVB其生存率为60%左右,再继续加大UVB的剂量,其生存率明显下降,故50J／m2的UVB是我们实验所选取的合适剂量。NIH3T3接受50J／m2后,继续培养不同的时间点,发现NIH3T3细胞在照射后的2h,4h,6h和12h其生存率变化显著,故我们选择这些时间点进行后面的miRNAs芯片分析。流式细胞仪分析显示：NIH3T3细胞在50J/m2 UVB照射后的12h,G1期细胞群的比例明显提高,而且出现了一个明显的凋亡峰和G1期细胞阻滞。NIH3T3细胞经50J/m2 UVB照射后继续培养12h,可见早期凋亡细胞,表现为细胞核为AO染色呈黄绿色荧光,浓聚成颗粒状；在细胞的一侧,可见细胞出芽。
miRNAs芯片结果显示,实验组细胞与对照组细胞差异表达的miRNA共30个(占11%),其中27个表达上调,3个表达下调。有趣的是,mmu-miR-365和mmu-miR-21显著上调,而mmu-miR-465在不同的时间点都下调。其差异表达均在2倍以上；Mmu-miR-let-7a, mmu-miR-24, mmu-miR-376b和mmu-miR-21的实时荧光定量RT-PCR验证结果与芯片表达结果基本一致。信号通路分析发现,miR-24参与MAPK等信号通路,miR-21参与Jak-STAT等信号通路。
利用TargetScan等多个靶基因的预测软件对miR-365的靶基因进行预测,结合GO分析,最后我们确定对NFIB、BCL2和CDK6这三个靶基因进行实验验证。在miR-365表达量较高的A431细胞中转染hsa-miR-365 inhibitor后,发现三个靶基因在RNA水平没有改变,而其蛋白水平,较对照组升高。这些结果说明,hsa-miR-365是在靶基因的蛋白水平发挥作用,而不影响靶基因的转录。将NFIB基因的3’UTR区克隆在荧光素酶报告载体psiCHECK-2的报告基因的下游,用Lipofectamine2000转染至A431细胞,DualLuciferaseTM检测荧光蛋白酶的活性,结果显示,相对于对照组,转染hsa-miR-365组的荧光素酶的表达量具有显著差异。这提示了miR-365是通过其NFIB的3’UTR发挥作用,且NFIB是其直接的靶基因。
Hsa-miR-365在皮肤鳞癌A431中表达是正常角质形成细胞的15倍,平板克隆形成实验结果显示,与空白对照组和错义转染组比较,hsa-miR-365反义片段转染的细胞增殖速度明显减慢(p<0.001),流式细胞仪结果显示三组的细胞周期分布没有明显差异(p>0.05)。Transwell小室结果显示,反义片段组细胞穿过聚碳酸酯膜的细胞数减少,差异具有显著性(p<0.001)。Boyden小室结果显示,反义片段组细胞细胞的侵袭能力显著降低(p<0.001)。
结论：我们的研究揭示了UVB辐射和miRNAs的联系,寻找出了在特定条件下对UVB敏感的miRNAs,这为研究受UVB调节的miRNA表达提供了基本的依据。我们进一步证明了NFIB是miR-365的靶基因,miR-365在蛋白水平抑制NFIB的表达,而不影响其转录,它们之间是通过NFIB 3'UTR相互作用的。hsa-miR-365在表皮癌细胞A431中高表达,将其抑制后显著降低了皮肤鳞癌细胞的体外迁移和侵袭能力,为研究miR-365在皮肤癌中的功能打了一定的基础。
Rencently, a class of non-coding RNAs called microRNAs (miRNAs), play an an important role in monitoring development phase changes of individual, in regulation of specific cell proliferation, differentiation and other aspects of the process. The role of miRNAs in UVB induced damages and diseases are gradually discovered by scientists.UVB relative miRNAs are found by miRNAs array, which is a start for studying UVB sensentive miRNAs. Therefore, targets genes of miRNAs were verified by bioinformatics and experiments. Furthermore, we analysed the role of miRNAs in epidermal carcinoma.The results provide the theory and experiment basis for the study of the UV-induced damage in the molecular mechanism and the role of miRNA in epidermal carcinoma.
Aim:To investigate the differentially expressed miRNAs and their target genes in NIH3T3 cells after UVB irradiation, which are useful for further studies on functions of miRNAs in UVB induced signal transduction pathway. Furthermore, to comfirm the target genes of hsa-miR-365 from structure, preparing for the study on function, to study the expression level of hsa-miR-365 in epidermal carcinoma and investigate the role of hsa-miR-365 inhibitor in A431 cells in vitro, which established the relationship between miR-365 and epidermal carcinoma and pointed out a new direction for studying epidermal carcinoma.
Methods:MTT, Flow Cytometry and AO/EB staining were used to detect cell morphological changes in NIH3T3. MicroRNA microarray was used to examine the differentially expressed miRNAs in NIH3T3 cells after UVB irradiation, and the discovered miRNAs were confirmed by real time RT-PCR assay. Targets predictions were performed by Microcosm and TargetScan and Potential target genes of these miRNAs were classified into different function categories with the GOstat software (http://gostat.wehi.edu.au/cgi-bin/goStat.pl).
Hsa-miR-365 target genes were predicted by availble data TargetScan. After hsa-miR-365 inhibitor were transfected A431 cells by Lipofectamine2000, Real-time qPCR, western blot were used to test the expression level at RNA and protein level. And Luciferase activty assay were performed to confirm the targets of hsa-miR-365 after hsa-miR-365 tansferred A431 cells.
Hsa-miR-365 expression level was test by real time RT-PCR assay in A431 cells. Corning Transwell Inserts and Boyden chamber were used to test the migration and invasion of A431 cells respectively. Meanwhile, pate clone forming assay and flow cytometry were used to examed the cell proliferation and apoptosis.
Results:the results of MTT showed that there was a great change in 50J/m2 UVB dose; when NIH3T3 cells were continued to culture 2h,4h,6h and 12h after 50J/m2 UVB irradiation, the change of survival rate was rapid in these piont. Morever, the results of flow cytometry showed there was an G1 arrest and an apoptosis peak at 12h after 50J/m2 UVB irradiation. AO/EB straining showed that typital apoptosis at 12h after 50J/m2 UVB irradiation. In some cells stained with EB, the nuclei exhibit bright condensed chromatin or fragmented chromatin, some cells showed apoptotic bleb phenomenon.
MicroRNA microarray showed that 30 miRNAs were differentially expressed, accounting for 11%, in which 27 up-regulated,3 down-regulated. Interestingly, the express level of mmu-miR-365 and mmu-miR-21 were more than six times, while mmu-miR-465 showed low levels of expression at all time points. The expression levels of mmu-miR-let-7a, mmu-miR-24, mmu-miR-376b and mmu-miR-21 were accordant with the results from real time RT-PCR. Single pathway analysis showed that miR-24 involed in MAPK signaling pathway, miR-21 involved in Jak-STAT signaling pathway.
To predict the target genes of miR-365 using TargetScan and other softwares, combined with GO analysis, we decided to confirmed the targets genes NFIB、BCL2 and CDK6 by experiment methods. After hsa-miR-365 inhibitors were transfected to A431 cells, we found that there was no change in the three target genes at RNA level, but their protein level increased compared with the control and negative control. Luciferase activty assay showed that there was a significant difference in the luciferase activty assay with miR-365 inhibitors among the three groups (p<0.05).
The expression level of hsa-miR-365 in A431 cells is more than 15 times as high as control.The results of vitro invasion assay showed that A431 cells with hsa-miR-356 inhibitors had significantly reduced in invasiveness as compared with control and negative control(F=111.709, P＜0.001). Furthermore, A431 cells with hsa-miR-356 inhibitor also caused a significant decrease of motility compared with control and negative control by use of Corning Transwell Inserts(F=41.732, P<0.001). All of these results showed low expression of miR-365 partially led to a downregulated migration and invasion of A431 cells. In addition, the ability to form colonies in plate of A431 cells with hsa-miR-365 inhibitors was significant reduced compareing that in control and negative control (F=30.077, P<0.001). However, the cell cycle distribution detected by flow cytometry is not significantly different among each other. These results revealed lower expression of miR-365 partially suppress proliferatin of A431 cells (P> 0.05).
Conclusions:Our research reveals the radiation between UVB radiation and miRNAs. We found the UVB sensentive miRNAs, which provides a basis for studying the regulation of miRNA expression in UVB radiation. Furthermore, we confirmed that NFIB is a direct target of miR-365, repressing the NFIB protein expression, not NFIB RNA. Hsa-miR-365 highly expressed in epidermal cancer cells A431 and hsa-miR-365 inhibitors significantly reduce skin cancer cell migration and invasion in vitro, laying a foundation for studying the function of skin cancer.
引文
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[6]Wang HQ, Quan T, He T, Franke TF, Voorhees JJ, Fisher GJ. Epidermal growth factor receptor-dependent, NF-kappaB-independent activation of the phosphatidylinositol 3-kinase/Akt pathway inhibits ultraviolet irradiation-induced caspases-3,-8, and-9 in human keratinocytes. J Biol Chem,2003,278 (46),45737-45745.
[7]Bell S, Degitz K, Quirling M, Jilg N, Page S, Brand K. Involvement of NF-kappaB signalling in skin physiology and disease. Cell Signal,2003, 15(1):1-7.
[8]Ting WW, Vest CD, Sontheimer R. Practical and experimental consideration of sun protection in dermatology. Int J Dermatol,2003,42(7),505-513.
[9]Cooper S, Ranger-Moore J, Bowden TG. Differential inhibition of UVB-induced AP-1 and NF-kappaB transactivation by components of the jun bZIP domain. Mol Carcinog,2005; 43(2),108-116.
[10]Imbert V, Rupec RA, Livolsi A, Pahl HL, Traenckner EB, Mueller-Dieckmann C, Farahifar D, Rossi B, Auberger P, Baeuerle PA, Peyron JF. Tyrosine phosphorylation of I kappa B-alpha activates NF-kappa B without proteolytic degradation of I kappa B-alpha. Cell,1996,86(5):787-798.
[11]Livolsi A, Busuttil V, Imbert V, Abraham RT, Peyron JF. Tyrosine phosphorylation-dependent activation of NF-kappa B. Requirement for p56 LCK and ZAP-70 protein tyrosine kinases. Eur J Biochem,2001,268(5): 1508-1515.
[12]Shaulian E, Karin M. AP-1 in cell proliferation and survival. Oncogene,2001; 20(19):2390-2400.
[13]Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol, 2002,4(5):E131-E136.
[14]Assefa Z, Garmyn M, Bouillon R, Merlevede W, Vandenheede JR, Agostinis P. Differential stimulation of ERK and JNK activities by ultraviolet B irradiation and epidermal growth factor in human keratinocytes. J Invest Dermato,1997, 108(6):886-891.
[15]Chen W, Bowden GT. Activation of p38 MAP kinase and ERK are required for ultraviolet-B induced c-fos gene expression in human keratinocytes. Oncogene,1999,18(52):7469-7476.
[16]Peus D, Vasa RA, Beyerle A, Meves A, Krautmacher C, Pittelkow MR. UVB activates ERK1/2 and p38 signaling pathways via reactive oxygen species in cultured keratinocytes. J Invest Dermato,1999,112(5):751-756.
[17]Bartel DP.MicroRNA:genomics, biogenesis, mechanism, and function. Cell, 2004,116(2):281-297
[18]郭玲,丁振华.微小RNA与细胞凋亡的研究进展.生理学进展,2007,38(4)：331-335
[19]刘琴,付汉江,郑晓飞.microRNA与细胞周期调控.军事医学科学院院刊,2008,32(5)：468-471
[20]Joris Pothof, Nicole S. Verkaik, Jan H.J. Hoeijmakers and Dik C. van Gent. MicroRNA responses and stress granule formation modulate the DNA damage response. Cell Cycle,2009,8(21),3462-3468
[21]Shin S, Cha HJ, Lee EM, Lee SJ, Seo SK, Jin HO, Park IC, Jin YW, An S, Alteration of miRNA profiles by ionizing radiation in A549 human non-small cell lung cancer cells, Int J Oncol,2009,35(1):81-86.
[22]Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell,2007,26(5):745-752.
[23]He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network, Nature,2007,447 (7148): 1130-1134.
[24]Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis, Mol Cell,2007,26(5):731-43.
[25]Hu H, Du L, Nagabayashi G, Seeger RC, ATM is down-regulated by N-Myc-regulated microRNA-421, Proc Natl Acad Sci U S A,2010,107(4): 1506-1511.
[26]Mikhailov A, Shinohara M, Rieder CL. The p38-mediated stress-activated checkpoint. A rapid response system for delaying progression through antephase and entry into mitosis, Cell Cycle,2005,4(1):57-62
[27]Sonkoly E, Wei T, Janson P C, et al. MicroRNAs:novel regulators involved in the pathogenesis of Psoriasis? PLoS ONE,2007,2(7):e610.
[28]Lowes M A, Bowcock A M, Krueger J G. Pathogenesis and therapy of psoriasis. Nature,2007,445(7130):866-873.
[29]Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, Itami S, Nickoloff BJ, DiGiovanni J. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med,2005,11(1):43-49.
[30]Yu J, Ryan DG, Getsios S, Oliveira-Fernandes M, Fatima A, Lavker RM. MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia. Proc Natl Acad Sci U S A,2008,105(49):19300-19305.
[31]Felicetti F, Errico MC, Bottero L, Segnalini P, Stoppacciaro A, Biffoni M, Felli N, Mattia G, Petrini M, Colombo MP, Peschle C, Care A.The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res,2008,68(8): 2745-2754.
[32]Zavadil J, Narasimhan M, Blumenberg M, Schneider RJ. Transforming growth factor-beta and microRNA:mRNA regulatory networks in epithelial plasticity. Cells Tissues Organs,2007,185(1-3):157-161.
[1]Bartel, DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell, 2004,116(2):281-297
[2]Plasterk, RH. Micro RNAs in animal development. Cell,2006,24(5):877-881.
[3]O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature,2005,435(7043):839-43.
[4]Inui M, Martello G, Piccolo S. MicroRNA control of signal transduction. Nat Rev Mol Cell Biol,2010,11(4):252-263.
[5]Situm M, Buljan M, Bulat V, Lugovic Mihic L, Bolanca Z, Simic D.The role of UV radiation in the development of basal cell carcinoma. Coll Antropol,2008, 32(Suppl 2):167-170.
[6]Ibuki Y, Akaike M, Toyooka T, Goto R. Aktl-mediated intracellular oxidation after UVB irradiation suppresses apoptotic cell death induced by cell detachment and serum starvation. Photochem Photobiol,2008,84(1):154-161.
[7]Hu QL, Ding ZH, Tan XH and Wang H. The characteristic of DNA cleavage of apoptotic NIH3T3 cells induced by ultraviolet irradiation.prog. Biochem. Biophy,1998,25(1),53-56
[8]Livak K J, Schmittgen T D. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2-ΔΔCT Method.Methods,2001,25(4):402-408.
[9]Xia W, Cao G, Shao N. Progress in miRNA target prediction and identification. Sci China C Life Sci,2009,52(12):1123-30.
[10]Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res, 2006,34(Database issue):140-144
[11]Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell,2003,115(7):787-798.
[12]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(5):495-500.
[13]Beissbarth T, Speed TP. GOstat:find statistically overrepresented Gene Ontologies within a group of genes. Bioinformatics,2004,20(9):1464-1465.
[14]Falcon S, Gentleman R. Using GOstats to test gene lists for GO term association. Bioinformatics,2007,23(2):257-258.
[15]Castoldi M, Schmidt S, Benes V, Noerholm M, Kulozik AE, Hentze MW, Muckenthaler MU. A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). RNA,2006,12(5):913-20.
[16]Braasch DA, Corey DR. Locked nucleic acid (LNA):fine-tuning the recognition of DNA and RNA. Chem Biol,2001,8(1):1-7.
[17]Tolstrup N, Nielsen PS, Kolberg JG, Frankel AM, Vissing H, Kauppinen S. OligoDesign:Optimal design of LNA (locked nucleic acid) oligonucleotide capture probes for gene expression profiling. Nucleic Acids Res,2003, 31(13):3758-62.
[18]Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene,2007,26(19):2799-803.
[19]Tran N, McLean T, Zhang X, Zhao CJ, Thomson JM, O'Brien C, Rose B. MicroRNA expression profiles in head and neck cancer cell lines. Biochem Biophys Res Commun,2007,358(1):12-17.
[20]Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A,2006, 103(7):2257-2261.
[21]Yu Z, Raabe T, Hecht NB. MicroRNA mirnl22a reduces expression of the posttranscriptionally regulated germ cell transition protein2 (Tnp2) messenger RNA (mRNA) by mRNA cleavage. Biol Reprod,2005,73(3):427-433.
[1]Bartel, DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell, 2004,116(2):281-297
[2]Bushati N, Cohen SM. MicroRNA functions. Annu Rev Cell Dev Biol,2007, 23:175-205.
[3]Wang Y, Stricker HM, Gou D, Liu L. MicroRNA:past and present. Front Biosci,2007,12:2316-29..
[4]Bentwich I. Prediction and validation of microRNAs and their targets. FEBS Lett,2005,579(26):5904-5910.
[5]Rajewsky N. microRNA target predictions in animals. Nat Genet,38 Suppl: S8-13.
[6]Maziere P, Enright AJ. Prediction of microRNA targes. Drug Disco v Today, 2007,12(11-12):452-458
[7]Doran J, Strauss WM. Bio informatic trends for the determination of miRNA-target interactions in mammals. DNA Cell Biol,2007,26(5):353-360.
[8]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(1):15-20.
[9]Didiano D, Hobert O. Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions. Nat Struct Mol Biol,2006,13(9):849-851.
[10]曹学武,陈正堂.miRNA靶基因实验验证的研究进展.重庆医学,2009,38(2)：211-213
[1]Felicetti F, Errico MC, Segnalini P, Mattia G, Care A. MicroRNA-221 and-222 pathway controls melanoma progression. Expert Rev Anticancer Ther, 2008,8(11):1759-65.
[2]Sun BK, Tsao H. Small RNAs in development and disease. J Am Acad Dermatol,2008,59(5):725-37.
[3]Sand M, Gambichler T, Sand D, Skrygan M, Altmeyer P, Bechara FG. MicroRNAs and the skin:tiny players in the body's largest organ. J Dermatol Sci,2009,53(3):169-75.
[4]de Gruijl FR. Skin cancer and solar UV radiation.Eur J Cancer,1999,35(14): 2003-2009.
[5]王文鑫,王晓彦.皮肤鳞状细胞癌及基底细胞癌的治疗进展.内蒙古医学杂志.2008,40(11)：1346-1349
[6]Yi R, Poy MN, Stoffel M, Fuchs E.A skin microRNA promotes differentiation by repressing'sternness'. Nature,2008,452(7184):225-229.
[7]Yu J, Ryan D G, Getsios S, et al. MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia. Proc Natl Acad Sci U S A,2008, 105(49):19300-19305.
[8]Felicetti F, Errico M C, Bottero L, et al. The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res,2008,68(8):2745-2754.
[1]闵玮,骆丹.中波紫外线与皮肤恶性肿瘤发生机制的研究进展.国外医学皮肤性病学分册,2004,30(3)：170-172.
[2]Bartel, DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell, 2004,116(2):281-297.
[3]Wang Y, Stricker HM, Gou D, Liu L. MicroRNA:past and present. Front Biosci,2007,12:2316-29..
[4]Bentwich I. Prediction and validation of microRNAs and their targets. FEBS Lett,2005,579(26):5904-5910.
[5]Rajewsky N. microRNA target predictions in animals. Nat Genet,38 Suppl: S8-13.
[6]Maziere P, Enright AJ. Prediction of microRNA targes. Drug Discov Today, 2007,12(11-12):452-458
[7]Doran J, Strauss WM. Bio informatic trends for the determination of miRNA-target interactions in mammals. DNA Cell Biol,2007,26(5):353-360.
[8]Shuji Fujita, Taiji Ito, Taketoshi Mizutani, Shigeru Minoguchi, Nobutake Yamamichi, Kouhei Sakurai and Hideo Iba. MiR-21 Gene Expression Triggered by AP-1 Is Sustained through a Double-Negative Feedback Mechanism. J. Mol. Biol.2008(3),378,492-504
[2]Epstein JH. Photocarcinogenesis, skin cancer, and aging. J Am Acad Dermatol, 1983; 9 (4),487-502.
[3]Fisher GJ, Kang S, Varani J, Bata-Csorgo Z, Wan Y, Datta S, Voorhees JJ. Mechanisms of photoaging and chronological skin aging. Arch Dermatol,2002, 138(11),1462-1470.
[4]Nicholson KM, Anderson NG. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal,2002,14(5):381-395.
[5]Huang C, Li J, Ding M, Leonard SS, Wang L, Castranova V, Vallyathan V, Shi X. UV Induces phosphorylation of protein kinase B (Akt) at Ser-473 and Thr-308 in mouse epidermal Cl 41 cells through hydrogen peroxide. J Biol Chem,2001,276(43),40234-40240.
[6]Wang HQ, Quan T, He T, Franke TF, Voorhees JJ, Fisher GJ. Epidermal growth factor receptor-dependent, NF-kappaB-independent activation of the phosphatidylinositol 3-kinase/Akt pathway inhibits ultraviolet irradiation-induced caspases-3,-8, and-9 in human keratinocytes. J Biol Chem,2003,278 (46),45737-45745.
[7]Bell S, Degitz K, Quirling M, Jilg N, Page S, Brand K. Involvement of NF-kappaB signalling in skin physiology and disease. Cell Signal,2003, 15(1):1-7.
[8]Ting WW, Vest CD, Sontheimer R. Practical and experimental consideration of sun protection in dermatology. Int J Dermatol,2003,42(7),505-513.
[9]Cooper S, Ranger-Moore J, Bowden TG. Differential inhibition of UVB-induced AP-1 and NF-kappaB transactivation by components of the jun bZIP domain. Mol Carcinog,2005; 43(2),108-116.
[10]Imbert V, Rupec RA, Livolsi A, Pahl HL, Traenckner EB, Mueller-Dieckmann C, Farahifar D, Rossi B, Auberger P, Baeuerle PA, Peyron JF. Tyrosine phosphorylation of I kappa B-alpha activates NF-kappa B without proteolytic degradation of I kappa B-alpha. Cell,1996,86(5):787-798.
[11]Livolsi A, Busuttil V, Imbert V, Abraham RT, Peyron JF. Tyrosine phosphorylation-dependent activation of NF-kappa B. Requirement for p56 LCK and ZAP-70 protein tyrosine kinases. Eur J Biochem,2001,268(5): 1508-1515.
[12]Shaulian E, Karin M. AP-1 in cell proliferation and survival. Oncogene,2001; 20(19):2390-2400.
[13]Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol, 2002,4(5):E131-E136.
[14]Assefa Z, Garmyn M, Bouillon R, Merlevede W, Vandenheede JR, Agostinis P. Differential stimulation of ERK and JNK activities by ultraviolet B irradiation and epidermal growth factor in human keratinocytes. J Invest Dermato,1997, 108(6):886-891.
[15]Chen W, Bowden GT. Activation of p38 MAP kinase and ERK are required for ultraviolet-B induced c-fos gene expression in human keratinocytes. Oncogene,1999,18(52):7469-7476.
[16]Peus D, Vasa RA, Beyerle A, Meves A, Krautmacher C, Pittelkow MR. UVB activates ERK1/2 and p38 signaling pathways via reactive oxygen species in cultured keratinocytes. J Invest Dermato,1999,112(5):751-756.
[17]Bartel DP.MicroRNA:genomics, biogenesis, mechanism, and function. Cell, 2004,116(2):281-297
[18]郭玲,丁振华.微小RNA与细胞凋亡的研究进展.生理学进展,2007,38(4)：331-335
[19]刘琴,付汉江,郑晓飞.microRNA与细胞周期调控.军事医学科学院院刊,2008,32(5)：468-471
[20]Joris Pothof, Nicole S. Verkaik, Jan H.J. Hoeijmakers and Dik C. van Gent. MicroRNA responses and stress granule formation modulate the DNA damage response. Cell Cycle,2009,8(21),3462-3468
[21]Shin S, Cha HJ, Lee EM, Lee SJ, Seo SK, Jin HO, Park IC, Jin YW, An S, Alteration of miRNA profiles by ionizing radiation in A549 human non-small cell lung cancer cells, Int J Oncol,2009,35(1):81-86.
[22]Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell,2007,26(5):745-752.
[23]He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network, Nature,2007,447 (7148): 1130-1134.
[24]Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis, Mol Cell,2007,26(5):731-43.
[25]Hu H, Du L, Nagabayashi G, Seeger RC, ATM is down-regulated by N-Myc-regulated microRNA-421, Proc Natl Acad Sci U S A,2010,107(4): 1506-1511.
[26]Mikhailov A, Shinohara M, Rieder CL. The p38-mediated stress-activated checkpoint. A rapid response system for delaying progression through antephase and entry into mitosis, Cell Cycle,2005,4(1):57-62
[27]Sonkoly E, Wei T, Janson P C, et al. MicroRNAs:novel regulators involved in the pathogenesis of Psoriasis? PLoS ONE,2007,2(7):e610.
[28]Lowes M A, Bowcock A M, Krueger J G. Pathogenesis and therapy of psoriasis. Nature,2007,445(7130):866-873.
[29]Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, Itami S, Nickoloff BJ, DiGiovanni J. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med,2005,11(1):43-49.
[30]Yu J, Ryan DG, Getsios S, Oliveira-Fernandes M, Fatima A, Lavker RM. MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia. Proc Natl Acad Sci U S A,2008,105(49):19300-19305.
[31]Felicetti F, Errico MC, Bottero L, Segnalini P, Stoppacciaro A, Biffoni M, Felli N, Mattia G, Petrini M, Colombo MP, Peschle C, Care A.The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res,2008,68(8): 2745-2754.
[32]Zavadil J, Narasimhan M, Blumenberg M, Schneider RJ. Transforming growth factor-beta and microRNA:mRNA regulatory networks in epithelial plasticity. Cells Tissues Organs,2007,185(1-3):157-161.
[1]Bartel, DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell, 2004,116(2):281-297
[2]Plasterk, RH. Micro RNAs in animal development. Cell,2006,24(5):877-881.
[3]O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature,2005,435(7043):839-43.
[4]Inui M, Martello G, Piccolo S. MicroRNA control of signal transduction. Nat Rev Mol Cell Biol,2010,11(4):252-263.
[5]Situm M, Buljan M, Bulat V, Lugovic Mihic L, Bolanca Z, Simic D.The role of UV radiation in the development of basal cell carcinoma. Coll Antropol,2008, 32(Suppl 2):167-170.
[6]Ibuki Y, Akaike M, Toyooka T, Goto R. Aktl-mediated intracellular oxidation after UVB irradiation suppresses apoptotic cell death induced by cell detachment and serum starvation. Photochem Photobiol,2008,84(1):154-161.
[7]Hu QL, Ding ZH, Tan XH and Wang H. The characteristic of DNA cleavage of apoptotic NIH3T3 cells induced by ultraviolet irradiation.prog. Biochem. Biophy,1998,25(1),53-56
[8]Livak K J, Schmittgen T D. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2-ΔΔCT Method.Methods,2001,25(4):402-408.
[9]Xia W, Cao G, Shao N. Progress in miRNA target prediction and identification. Sci China C Life Sci,2009,52(12):1123-30.
[10]Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res, 2006,34(Database issue):140-144
[11]Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell,2003,115(7):787-798.
[12]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(5):495-500.
[13]Beissbarth T, Speed TP. GOstat:find statistically overrepresented Gene Ontologies within a group of genes. Bioinformatics,2004,20(9):1464-1465.
[14]Falcon S, Gentleman R. Using GOstats to test gene lists for GO term association. Bioinformatics,2007,23(2):257-258.
[15]Castoldi M, Schmidt S, Benes V, Noerholm M, Kulozik AE, Hentze MW, Muckenthaler MU. A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). RNA,2006,12(5):913-20.
[16]Braasch DA, Corey DR. Locked nucleic acid (LNA):fine-tuning the recognition of DNA and RNA. Chem Biol,2001,8(1):1-7.
[17]Tolstrup N, Nielsen PS, Kolberg JG, Frankel AM, Vissing H, Kauppinen S. OligoDesign:Optimal design of LNA (locked nucleic acid) oligonucleotide capture probes for gene expression profiling. Nucleic Acids Res,2003, 31(13):3758-62.
[18]Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene,2007,26(19):2799-803.
[19]Tran N, McLean T, Zhang X, Zhao CJ, Thomson JM, O'Brien C, Rose B. MicroRNA expression profiles in head and neck cancer cell lines. Biochem Biophys Res Commun,2007,358(1):12-17.
[20]Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A,2006, 103(7):2257-2261.
[21]Yu Z, Raabe T, Hecht NB. MicroRNA mirnl22a reduces expression of the posttranscriptionally regulated germ cell transition protein2 (Tnp2) messenger RNA (mRNA) by mRNA cleavage. Biol Reprod,2005,73(3):427-433.
[1]Bartel, DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell, 2004,116(2):281-297
[2]Bushati N, Cohen SM. MicroRNA functions. Annu Rev Cell Dev Biol,2007, 23:175-205.
[3]Wang Y, Stricker HM, Gou D, Liu L. MicroRNA:past and present. Front Biosci,2007,12:2316-29..
[4]Bentwich I. Prediction and validation of microRNAs and their targets. FEBS Lett,2005,579(26):5904-5910.
[5]Rajewsky N. microRNA target predictions in animals. Nat Genet,38 Suppl: S8-13.
[6]Maziere P, Enright AJ. Prediction of microRNA targes. Drug Disco v Today, 2007,12(11-12):452-458
[7]Doran J, Strauss WM. Bio informatic trends for the determination of miRNA-target interactions in mammals. DNA Cell Biol,2007,26(5):353-360.
[8]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(1):15-20.
[9]Didiano D, Hobert O. Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions. Nat Struct Mol Biol,2006,13(9):849-851.
[10]曹学武,陈正堂.miRNA靶基因实验验证的研究进展.重庆医学,2009,38(2)：211-213
[1]Felicetti F, Errico MC, Segnalini P, Mattia G, Care A. MicroRNA-221 and-222 pathway controls melanoma progression. Expert Rev Anticancer Ther, 2008,8(11):1759-65.
[2]Sun BK, Tsao H. Small RNAs in development and disease. J Am Acad Dermatol,2008,59(5):725-37.
[3]Sand M, Gambichler T, Sand D, Skrygan M, Altmeyer P, Bechara FG. MicroRNAs and the skin:tiny players in the body's largest organ. J Dermatol Sci,2009,53(3):169-75.
[4]de Gruijl FR. Skin cancer and solar UV radiation.Eur J Cancer,1999,35(14): 2003-2009.
[5]王文鑫,王晓彦.皮肤鳞状细胞癌及基底细胞癌的治疗进展.内蒙古医学杂志.2008,40(11)：1346-1349
[6]Yi R, Poy MN, Stoffel M, Fuchs E.A skin microRNA promotes differentiation by repressing'sternness'. Nature,2008,452(7184):225-229.
[7]Yu J, Ryan D G, Getsios S, et al. MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia. Proc Natl Acad Sci U S A,2008, 105(49):19300-19305.
[8]Felicetti F, Errico M C, Bottero L, et al. The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res,2008,68(8):2745-2754.
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