缺氧人视网膜色素上皮细胞株ARPE-19差异MicroRNA表达及鉴定
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摘要
第一部分缺氧人视网膜色素上皮细胞株ARPE-19表达特性
目的观察缺氧对人视网膜色素上皮株ARPE-19的细胞形态、增殖以及对其分泌的血管内皮生长因子和色素上皮衍生因子表达的影响。
方法将ARPE-19细胞分别置正常和缺氧环境中培养0hr、8hr、24hr、48hr后,MTT比色法检测ARPE-19细胞的增殖;Hochest染色观察细胞形态、检测细胞凋亡率;流式细胞仪检测细胞凋亡率;选取缺氧24hr的细胞,RT-PCR检测VEGF mRNA及PEDF mRNA的表达,经计算机图像处理,定量分析。
结果缺氧组的MTT实验吸光度(A值)明显低于正常组,缺氧48小时时差异最显著(P＜0.001);Hochest染色及流式细胞仪检测细胞凋亡率,缺氧24小时时其凋亡率明显高于正常组(P＜0.001);RT-PCR检测VEGF mRNA表达缺氧组明显高于正常组,PEDF mRNA表达缺氧组明显低于正常组。
结论缺氧可加剧ARPE-19细胞的凋亡,破坏VEGF与PEDF表达的平衡,调节视网膜色素上皮细胞的活性是抑制脉络膜新生血管生成的关键。
第二部分缺氧人视网膜色素上皮细胞株ARPE-19 MicroRNA的差异表达
目的MicroRNA在调控基因表达及组织功能等方面发挥着重要的作用。但对其在眼科领域对于CNV的形成的调控却研究的很少。本部分目的在于筛选CNV形成相关的MicroRNA。
方法视网膜色素上皮细胞株ARPE-19置缺氧环境24小时后,抽提RNA进行MicroRNA芯片(LC science公司)检测。对于信号值高于1000的差异MicroRNA利用实时定量PCR(q-PCR)进行检测。
结果具有显著性差异(即p值＜0.01)表达转录子共有42条miRNA,其中低氧后上调的18条,下调的24条,信号值差异位居前十位的MicroRNA分别为Mir-1、Mir-1469、Mir-663、Mir-1915、Mir-29c、Mir-574-5p、Mir-638、Mir-29b-1、Mir-1308、Mir-10a,其中除Mir-1、Mir-29c、Mir-1308表现为下调外,其余均表现为上调。信号值高于1000的MicroRNA共有28条,其中Mir-638、Mir-1308、Mir-125b、Mir-155、Mir-30c、Mir-125a-5p与芯片检测结果相一致,Mir-155表达异常最为显著。
结论视网膜色素上皮细胞株ARPE-19细胞经缺氧处理后,很多MicroRNA发生差异性表达,可能与CNV的形成密切相关。
第三部分MicroRNA-155转染人视网膜色素上皮细胞株ARPE-19活性初步研究
目的:探讨对于视网膜色素上皮细胞株ARPE-19细胞,Mir-155是否具有一定的抗缺氧活性,并对CNV的形成具有一定的调节作用。
方法:Mir-155转染视网膜色素上皮细胞株ARPE-19细胞后,将其置缺氧环境0hr、8hr、24hr、48hr后,MTT比色法检测ARPE-19细胞的增殖,流式细胞仪检测细胞凋亡率。
结果:转染组的MTT实验吸光度(A值)高于未转染组,缺氧48小时时差异最明显;流式细胞仪检测细胞凋亡率,转染组凋亡率低于未转染组(P＜0.001),缺氧48小时时差异最明显。
结论:Mir-155转染视网膜色素上皮细胞株ARPE-19细胞后,具有一定的抗缺氧活性,对CNV的形成具有一定的调节作用。
Part 1 Expression character of Hopoxia Human Retinal Pigment Epithelial Cell Line ARPE-19
Objective To study the influence of hypoxia on appearance and proliferation of human retinal pigment epithelial(RPE)cells and expression of VEGF and PEDF.
Methods The ARPE-19 cells were put into normal and hypoxic chamber respectively.After 0hr、8hr、24hr、48hr,the proliferation of ARPE-19 cells was evaluated by[3-(4,5-dimethylthiazole-2yl)-2,5-diphenyl tetrazolium bromid, MTT]-test.Apoptosis rate of ARPE-19 were detected by hochest staining and flow cytometry.After 24 hours,the VEGF mRNA and PEDF mRNA were detected by RT-PCR.Image processing and quantitative analysis were applied with computer.
Results The value detected by MTT in the hypoxia groups were lower than that in the normal group,especially at 48h point(P＜0.001).Apoptosis rate of ARPE-19 that determined by hochest staining and flow cytometry were higher in the hypoxia groups,especially at 24h point(P＜0.001).The expression of VEGF mRNA in ARPE-19 cells increased obviously under hypoxia,and the expression of PEDF mRNA in ARPE-19 cells decreased obviously under hypoxia.
Conclusion Hypoxia can stimulate the apoptosis of ARPE-19 cells,destroy the balance of VEGF and PEDF expression,The results indicate that controlling the activity of RPE during hypoxia is essential to inhibit the formation of choroidal neovascularization.
Part 2 Expression of Differencial MicroRNA in Hopoxia Human Retinal Pigment Epithelial Cell Line ARPE-19
Objective MicroRNA(miRNA)play a global role in regulating gene expression and have important tissue-specific functions.But little is known about their role in the emerge of CNV in region of ophthalmology.The purpose of this study was to find those different miRNAs that predicted to target genes involved in emerge of CNV.
Methods Retinal pigment epithelium cell line ARPE-19 were put into hypoxic chamber for 24 hours and RNA were extracted for detection further.Different miRNAs were predicted using Microarray assay(LC Sciences)with RNA that extracted from ARPE-19 cells.Different miRNAs that signal numerical value above 1000 were verificated by quantitative PCR(q-PCR).
Results 42 miRNAs were predicted to target emerge of CNV,within these miRNAs 18 miRNAs expressed as up-regulation,and 24 miRNAs expressed as down-regulation,that ten highest signal numerical value include Mir-1、Mir-1469、Mir-663、Mir-1915、Mir-29c、Mir-574-5p、Mir-638、Mir-29b-1、Mir- 1308、Mir-10a,within these miRNAs Mir-1、Mir- 29c、Mir- 1308 expressed as down-regulation,the others expressed as up-regulation.Within 28 miRNAs that signal numerical value above 1000 included Mir-638、Mir-1308、Mir-125b、Mir-155、Mir-30c、Mir-125a-5p which expressed coincidence with the results of Microarray assay.Through verification Mir-155 expressed as the most significant. Conclusion Many miRNAs likely to regulate genes important for emerge of CNV were present in the ARPE-19 in hypoxic chamber.
ARPE-19 after Mir-155 transfection
Objective The purpose of this study was to find whether Mir-155 has some activity of anti-hypoxia and play very important role in emerge of CNV to human retinal pigment epithelium cell line ARPE- 19.
Methods The ARPE-19 cells were transfected with Mir-155,and then put into hypoxic chamber for 0hr、8hr、24hr、48hr,the proliferation of ARPE-19 cells was evaluated by[3-(4,5-dimethylthiazole-2yl)-2,5-diphenyl tetrazolium bromid, MTT]-test.Apoptosis rate of ARPE-19 were detected by flow cytometry. Results The value detected by MTT in the transfected groups were higher, especially at 48h point.Apoptosis rate of ARPE-19 that determined by flow cytometry were lower in the transfected groups(P＜0.001),especially at 48h point.
Conclusion Mir-155 enduce some activity of anti-hypoxia after transfection within ARPE- 19 and play very important role in emerge of CNV.
目的观察缺氧对人视网膜色素上皮株ARPE-19的细胞形态、增殖以及对其分泌的血管内皮生长因子和色素上皮衍生因子表达的影响。
方法将ARPE-19细胞分别置正常和缺氧环境中培养0hr、8hr、24hr、48hr后,MTT比色法检测ARPE-19细胞的增殖;Hochest染色观察细胞形态、检测细胞凋亡率;流式细胞仪检测细胞凋亡率;选取缺氧24hr的细胞,RT-PCR检测VEGF mRNA及PEDF mRNA的表达,经计算机图像处理,定量分析。
结果缺氧组的MTT实验吸光度(A值)明显低于正常组,缺氧48小时时差异最显著(P＜0.001);Hochest染色及流式细胞仪检测细胞凋亡率,缺氧24小时时其凋亡率明显高于正常组(P＜0.001);RT-PCR检测VEGF mRNA表达缺氧组明显高于正常组,PEDF mRNA表达缺氧组明显低于正常组。
结论缺氧可加剧ARPE-19细胞的凋亡,破坏VEGF与PEDF表达的平衡,调节视网膜色素上皮细胞的活性是抑制脉络膜新生血管生成的关键。
第二部分缺氧人视网膜色素上皮细胞株ARPE-19 MicroRNA的差异表达
目的MicroRNA在调控基因表达及组织功能等方面发挥着重要的作用。但对其在眼科领域对于CNV的形成的调控却研究的很少。本部分目的在于筛选CNV形成相关的MicroRNA。
方法视网膜色素上皮细胞株ARPE-19置缺氧环境24小时后,抽提RNA进行MicroRNA芯片(LC science公司)检测。对于信号值高于1000的差异MicroRNA利用实时定量PCR(q-PCR)进行检测。
结果具有显著性差异(即p值＜0.01)表达转录子共有42条miRNA,其中低氧后上调的18条,下调的24条,信号值差异位居前十位的MicroRNA分别为Mir-1、Mir-1469、Mir-663、Mir-1915、Mir-29c、Mir-574-5p、Mir-638、Mir-29b-1、Mir-1308、Mir-10a,其中除Mir-1、Mir-29c、Mir-1308表现为下调外,其余均表现为上调。信号值高于1000的MicroRNA共有28条,其中Mir-638、Mir-1308、Mir-125b、Mir-155、Mir-30c、Mir-125a-5p与芯片检测结果相一致,Mir-155表达异常最为显著。
结论视网膜色素上皮细胞株ARPE-19细胞经缺氧处理后,很多MicroRNA发生差异性表达,可能与CNV的形成密切相关。
第三部分MicroRNA-155转染人视网膜色素上皮细胞株ARPE-19活性初步研究
目的:探讨对于视网膜色素上皮细胞株ARPE-19细胞,Mir-155是否具有一定的抗缺氧活性,并对CNV的形成具有一定的调节作用。
方法:Mir-155转染视网膜色素上皮细胞株ARPE-19细胞后,将其置缺氧环境0hr、8hr、24hr、48hr后,MTT比色法检测ARPE-19细胞的增殖,流式细胞仪检测细胞凋亡率。
结果:转染组的MTT实验吸光度(A值)高于未转染组,缺氧48小时时差异最明显;流式细胞仪检测细胞凋亡率,转染组凋亡率低于未转染组(P＜0.001),缺氧48小时时差异最明显。
结论:Mir-155转染视网膜色素上皮细胞株ARPE-19细胞后,具有一定的抗缺氧活性,对CNV的形成具有一定的调节作用。
Part 1 Expression character of Hopoxia Human Retinal Pigment Epithelial Cell Line ARPE-19
Objective To study the influence of hypoxia on appearance and proliferation of human retinal pigment epithelial(RPE)cells and expression of VEGF and PEDF.
Methods The ARPE-19 cells were put into normal and hypoxic chamber respectively.After 0hr、8hr、24hr、48hr,the proliferation of ARPE-19 cells was evaluated by[3-(4,5-dimethylthiazole-2yl)-2,5-diphenyl tetrazolium bromid, MTT]-test.Apoptosis rate of ARPE-19 were detected by hochest staining and flow cytometry.After 24 hours,the VEGF mRNA and PEDF mRNA were detected by RT-PCR.Image processing and quantitative analysis were applied with computer.
Results The value detected by MTT in the hypoxia groups were lower than that in the normal group,especially at 48h point(P＜0.001).Apoptosis rate of ARPE-19 that determined by hochest staining and flow cytometry were higher in the hypoxia groups,especially at 24h point(P＜0.001).The expression of VEGF mRNA in ARPE-19 cells increased obviously under hypoxia,and the expression of PEDF mRNA in ARPE-19 cells decreased obviously under hypoxia.
Conclusion Hypoxia can stimulate the apoptosis of ARPE-19 cells,destroy the balance of VEGF and PEDF expression,The results indicate that controlling the activity of RPE during hypoxia is essential to inhibit the formation of choroidal neovascularization.
Part 2 Expression of Differencial MicroRNA in Hopoxia Human Retinal Pigment Epithelial Cell Line ARPE-19
Objective MicroRNA(miRNA)play a global role in regulating gene expression and have important tissue-specific functions.But little is known about their role in the emerge of CNV in region of ophthalmology.The purpose of this study was to find those different miRNAs that predicted to target genes involved in emerge of CNV.
Methods Retinal pigment epithelium cell line ARPE-19 were put into hypoxic chamber for 24 hours and RNA were extracted for detection further.Different miRNAs were predicted using Microarray assay(LC Sciences)with RNA that extracted from ARPE-19 cells.Different miRNAs that signal numerical value above 1000 were verificated by quantitative PCR(q-PCR).
Results 42 miRNAs were predicted to target emerge of CNV,within these miRNAs 18 miRNAs expressed as up-regulation,and 24 miRNAs expressed as down-regulation,that ten highest signal numerical value include Mir-1、Mir-1469、Mir-663、Mir-1915、Mir-29c、Mir-574-5p、Mir-638、Mir-29b-1、Mir- 1308、Mir-10a,within these miRNAs Mir-1、Mir- 29c、Mir- 1308 expressed as down-regulation,the others expressed as up-regulation.Within 28 miRNAs that signal numerical value above 1000 included Mir-638、Mir-1308、Mir-125b、Mir-155、Mir-30c、Mir-125a-5p which expressed coincidence with the results of Microarray assay.Through verification Mir-155 expressed as the most significant. Conclusion Many miRNAs likely to regulate genes important for emerge of CNV were present in the ARPE-19 in hypoxic chamber.
ARPE-19 after Mir-155 transfection
Objective The purpose of this study was to find whether Mir-155 has some activity of anti-hypoxia and play very important role in emerge of CNV to human retinal pigment epithelium cell line ARPE- 19.
Methods The ARPE-19 cells were transfected with Mir-155,and then put into hypoxic chamber for 0hr、8hr、24hr、48hr,the proliferation of ARPE-19 cells was evaluated by[3-(4,5-dimethylthiazole-2yl)-2,5-diphenyl tetrazolium bromid, MTT]-test.Apoptosis rate of ARPE-19 were detected by flow cytometry. Results The value detected by MTT in the transfected groups were higher, especially at 48h point.Apoptosis rate of ARPE-19 that determined by flow cytometry were lower in the transfected groups(P＜0.001),especially at 48h point.
Conclusion Mir-155 enduce some activity of anti-hypoxia after transfection within ARPE- 19 and play very important role in emerge of CNV.
引文
1.Chen PY,Meister G.microRNA-guided posttranscriptional gene regulation.BiolChem,2005,386(12):1205-1218.
2.Esquela-KerscherA,Slack FJ.Oncomirs-microRNAs with a role in cancer.NatRev Cancer,2006,6 (4):259-269.
3.Slack FJ,Weidhaas JB.MicroRNAs as a potentialmagic bullet in cancer.FutOncol,2006,2 (1):73-82.
4.Makarev E,Spence JR,Del Rio-Tsonis K,Tsonis PA.Identification of microRNAs and other small RNAs from the adult newt eye.Mol Vis,2006,15(12):1386-1391.
5.Ryan DG,Oliveira-Fernandes M,Lavker RM.MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity.Mol Vis,2006,17(12):1175-1184.
6.Karah M,Peluso I,Marigo V,Banfi S.Identification and characterization of microRNAS expressed in the mouse eye.Invest Ophthalmol Vis Sci,2007,48(2):509-515.
7.Kuehbacher,A.et al.Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis.Circ.Res,2007,101 (1):59-68.
8.Suarez,Y.et al.Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells.Circ.Res,2007,100 (8):1164-1173.
9.Poliseno,L.et al.MicroRNAs modulate the angiogenic properties of HUVECs.Blood,2006,108 (9):3068-3071.
10.Hua,Z.et al.MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia.PLoS ONE,2006,27(1):116.
11.Meister G,Landthaler M,Dorsett Y,Tuschl T.Sequence-specific inhibition of microRNA-and siRNA-induced RNA silencing.RNA,2004,10(3):544-550.
12.Esau C,Davis S,Murray SF,Yu XX,Pandey SK,Pear M et al.miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting.Cell Metab,2006,3(2):87-98.
13.Pham I,Uchida T,Planes C,Ware LB,Kaner R,MatthayMA,et al.Hypoxiaup regulates V EGF expression in alveolr epithelial cells in vitro and in vivo[J].Am J Physiol Lung Cell Mol P hysiol 2002,283(5):1133-1142.
14.Takekoshi K,Isobe K,Yashiro T,Hara H,Ishii K,Kawakami Y,et al.Expression of vascular endothelial growth factor (VEGF)and its cognate receptors in human pheochromocytomas [J].Life Sci 2004,74(7):863-871.
15.Dawson DW,Volpert OV,Gillis P,et al.Pigment epithelium-derived factor:a potent inhibitor of angiogenesis.[J].Science 1999,285(5425):245-248.
16.Grossniklaus HE,Ling JX,Wallace TM,Dithmar S,Lawson DH,Cohen C,et al.Macroplage and retinal pigment epiyhelium expression of angiogenic cytokines in choroidal neovascularization.Mol Vis 2002,21(8):! 19-126.
1.曲冬懿,何守志.VEGF-B 及其受体 Flt-1在氪激光诱导的大鼠脉络膜新生血管中的表达.眼科新进展,2005,25(2):123-126.
2.曲冬懿何守志.血管生成素-2及其受体在脉络膜新生血管中的表达.眼科研究,2005,23(3):249-251.
3.赵世红,何守志.碱性成纤维细胞生长因子及其受体 FGFR1在脉络膜新生血管中的表达.眼科研究,2003,21(3):234-237.
4.史雪辉,何守志.转化生长因子β及其受体在实验性脉络膜新生血管中的表达及意义.眼科,2006,15(4):262-266.
5.史雪辉,何守志,陈学国.色素上皮衍生因子对氪激光诱导大鼠脉络膜新生血管的抑制作用.中国激光医学杂志,2006,15(2):74-78.
6.陈松,韩梅.老年性黄斑变性黄斑部脉络膜血循环研究[J].中华眼底病杂志2002;18(2):116-118.
7.Grunwald JE et al.Vascular endothelial growth factor and severity of nonproliferative diabetic retinopathy mediate retinal hemodynamics in vivo:a potential role for vascular endothelial growth factor in the progression of nonproliferative diabetic retinopathy.Invest Ophthalmol Vis Sci,1998;39(2):385.
8.Grossniklaus HE,Ling JX,Wallace TM,Dithmar S,Lawson DH,Cohen C,et al.Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization.Mol Vis.2002,21(8):119-126.
9.Bouck N.PEDF:antiangiogenic guideline of ocular function.Trends Mol Med,2002,8(7):330-334.
10.Holekamp NM,BouckN,Volpert O.Pigment epithelium-derived factor is deficient in the vitreous of patients with choroidal neovascularization due to age-related macular degeneration.Am J Ophthalmol,2002,134(2):220-227.
11.Duh EJ,Yang HS,Suzuma I,et al.Pigment epithelium derived factor supp resses ischemia induced retinal neovascularization and VEGF-induced migration and growth [J].Invest Ophthalmol Vis Sci,2002,43 (3):821-829.
12.Dawson DW,Volpert OV,Gillis P,et al.Pigment epithelium derived factor:a potent inhibitor of angiogensis[J].Science,1999,285(5425):245-248.
13.Tombran-Tink J,Shivaram SM,Chader GJ,et al.Expression,secretion,and age-related down regulation of pigment epithelium derived factor,a serpin with neurotrophic activity [J].J Neurosci,1995,15(7 Pt l):4992-5003.
14.Alberdi E,Aymerich MS,Becerra SP.Binding of pigment epithelium derived factor(PEDF)to retinoblastoma cells and cerebellar granule neurons.Evidence for a PEDF receptor[J].J Biol C hem,1999,274(44):31605-31612.
15.Kidner CA,Martienssen,RA.Macro effects of microRNAs in plants.Trends Genet,2003,19(1):13-16.
16.Kuehbacher,A.et al.Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis.Circ.Res,2007,101(1):59-68.
17.Suarez,Y.et al.Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells.Circ.Res,2007,100(8):1164-1173.
18.Poliseno,L.et al.MicroRNAs modulate the angiogenic properties of HUVECs.Blood,2006,108(9):3068-3071.
19.(a)Gao,X.,Gulari,E.,and Zhou,X.(2004)In situ synthesis of oligonucleotide microarrays.Biopolymers 73,579-596;(b)Zhu,Q.,Hong,A.,Sheng,N.,Zhang,X.,Jun,K.-Y.,Srivannavit,O.,Gulari,E.,Gao,X.,and Zhou,X.(2006)Microfluidic biochip for nucleic acid and protein analysis,in Methods Mol.Biol.Ed.Rampal,J.B.in press.
20.Bolstad,B.M.,Irizarry,R.A.,Astrandand,M.,Speed,T.P.A comparison of normalization methods for high density oligonucleotide array data based on variance and bias.Bioinformatics.2003,19(2),185-193.
21.Lee RC,Feinbaum RL,Ambros V.The C.elegans heteroch ronic gene lin-4 encodes small RNA with antisense complementarity to lin-14.Cell,1993,75(5):843-854.
22.ReinhartBJ,Slack FJ,BassonM,et al.The 21 nucletide let-7 RNA regulates developmental timing in caenorhabd it is elegans.Nature,2000,403(6772):901-906.
23.Carthew RW.Gene rgulation by microRNAs.Curr Opin GenetDev,2006,16(2):203-208.
24.Esquela-KerscherA,Slack FJ.Oncomirs-microRNAs with a role in cancer.Nat Rev Cancer,2006,6(4):259-269.
25.Slack FJ,Weidhaas JB.MicroRNAs as a potentialmagic bullet in cancer.FutureOncol,2006,2(1):73-82.
26.Ryan DG,Oliveira-Fernandes M,Lavker RM.MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity.Mol Vis,2006,17(12):1175-1184.
27.Frederikse PH,Donnelly R,Partyka LM.miRNA and Dicer in the mammalian lens:expression of brain-specific miRNAs in the lens.Histochem Cell Biol,2006,126(1):1-8.
28.Karah M,Peluso I,Marigo V,Banfi S.Identification and characterization of microRNAS expressed in the mouse eye.Invest Ophthalmol Vis Sci,2007,48(2):509-515.
29.Loscher CJ,Hokamp K,Kenna PF,Ivens AC,Humphries P,Palfi A,Farrar GJ.Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa.Genome Biol.2007,8(11):248.
30.Worley LA,Long MD,Onken MD,Harbour JW.Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling.Melanoma Res.2008,18(3):184-190.
31.Bilen J,Liu N,Bonini NM.A new role for microRNA pathways:modulation of degeneration induced by pathogenic human disease proteins.Cell Cycle.2006,5(24):2835-2838.
32.Kuehbacher,A.et al.Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis.Circ Res,2007,101(1):59-68.
33.Suarez,Y.et al.Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells.Circ Res,2007,100(8):1164-1173.
34.Pohseno,L.et al.MicroRNAs modulate the angiogenic properties of HUVECs.Blood,2006,108(9):3068-3071.
35.Ritu Kulshreshtha,Manuela Ferracin,Sylwia E,Wojcik,et al.A MicroRNA Signature of Hypoxia,Molecular and cellular biology,2007,27(5):1859-1867.
36.Shen J,Yang X,Xie B,Chen Y,Swaim M,Hackett SF,Campochiaro PA.MicroRNAs regulate ocular neovascularization.Mol Ther.2008,16(7):1208-1216.
37.Zhong Hual.a,Qing Lvl.a,WenbinYe.MiRNA-Directed Regulation of VEGF and Other Angiogenic Factors under Hypoxia,www.plosone.org,2006,Issue l,el16:l-13.
38.Chen JF,Mandel EM,Thomson JM,Wu Q,Callis TE,Hammond SM et al.The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.Nat Genet,2006;38(2):228-233.
39.Poliseno L.et al.MicroRNAs modulate the angiogenic properties of HUVECs.Blood,2006,108(9):3068-3071.
40.Roccaro AM,Sacco A,Chen C.microRNA expression in the biology,prognosis and therapy of Waldenstrom macroglobulinemia.Blood.2009,113(18):4391-4402.
41.Teng G,Papavasihou FN.Shhh! Silencing by microRNA-155.Philos Trans R Soc LondB Biol Sci.2009,12;364(1517):631-637.
42.Yang H,He L,Zhao J,Coppola D,Dalton WS,Cheng JQ.MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA.Mol Cell Biol.2008,28(22):6773-6784.
1、Kidner CA,Martienssen RA.Macro effects of microRNAs in plants.Trends Genet,2003,19(1):13-16.
2、Denlil AM,Tops BB,et al.Processing of primary microRNAs by the Microprocessor complex.Nature,2004,432(7014):231-235.
3、Bartel,DP.MicroRNAs:genomics,biogenesis,mechanism,and function.Cell,2004,116(2):281-297.
4、Chen PY,Meister G.microRNA-guided posttranscriptional generegulation.BiolChem,2005,386(12):1205-1218.
5、Liu J,Gao Y,et al.Effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation.World J Gastroenterol,2005,11(8):1161-1166.
6、Valencia-Sanchez M.A.,Liu J.,Hannon G.J.,Parker,R.Control of translation and mRNA degradation by miRNAs and siRNAs.Genes Dev,2006,20(5):515-524.
7、Esquela-KerscherA,Slack FJ.Oncomirs-microRNAs with a role in cancer.NatRev Cancer,2006,6(4):259-269.
8、Slack F J,Weidhaas JB.MicroRNAs as a potentialmagic bullet in cancer.FutOncol,2006,2(1):73-82.
9、Shingara J,Keiger K,Shelton J,Laosinchai-Wolf W,Powers P,Conrad R et al.An optimized isolation and labeling platform for accurate microRNA expression profiling.RNA,2005,11(9):1461-1470.
10、Lu J,Getz G,Miska EA,Alvarez-Saavedra E,Lamb J,Peck D et al.MicroRNA expression profiles classify human cancers.Nature,2005,435(7043):834-838.
11、Neely LA,Patel S,Garver J,Gallo M,Hackett M,McLaughlin S et al.A single-molecule method for the quantitation of microRNA gene expression.Nat Methods,2006,3(1):41^16.
12、Mattie MD,Benz CC,Bowers J,Sensinger K,Wong L,Scott GK et al.Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies.Mol Cancer,2006,19(5):24.
13、Schratt GM,Tuebing F,Nigh EA,Kane CG,Sabatini ME,Kiebler M et al.A brain-specific microRNA regulates dendritic spine development.Nature,2006,439(7074):283-289.
14、Chen JF,Mandel EM,Thomson JM,Wu Q,Callis TE,Hammond SM et al.The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.Nat Genet,2006,38(2):228-233.
15、Hwang HW,Mendell JT.MicroRNAs in cell proliferation,cell death and tumorigenesis.Br J Cancer,2006,94(6):776-780.
16、Chen CZ.MicroRNAs as oncogenes and tumor suppressors.N Engl J Med,2005,353(17):1768-1771.
17、Cimmino A,Calin GA,Fabbri M,Iorio MV,Ferracin M,Shimizu M et al.miR-15 and miR-16 induce apoptosis by targeting BCL2.Proc Natl Acad Sci USA,2005,102(39):13944-13949.
18、Johnson SM,Grosshans H,Shingara J,Byrom M,Jarvis R,Cheng A et al.RAS is regulated by the let-7 microRNA family.Cell,2005,120(5):635-647.
19、Hayashita Y,Osada H,Tatematsu Y,Yamada H,Yanagisawa K,Tomida S et al.A polycistronic microRNA cluster,miR-17-92,is overexpressed in human lung cancers and enhances cell proliferation.Cancer Res,2005,65(21):9628-9632.
20、Chan JA,Krichevsky AM,Kosik KS.MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells.Cancer Res,2005,65(14):6029-6033.
21、 Eis PS,Tam W,Sun L,Chadburn A,Li Z,Gomez MF et al.Accumulation of miR-155 and BIC RNA in human B cell lymphomas.Proc Natl Acad Sci USA,2005,102(10):3627-3632.
22、Calin GA,Ferracin M,Cimmino A,Di Leva G,Shimizu M,Wojcik SE et al.A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia.N Engl J Med,2005,353(17):1793-1801.
23、Volinia S,Calin GA,Liu CG,Ambs S,Cimmino A,Petrocca F et al.A microRNA expression signature of human solid tumors defines cancer gene targets.Proc Natl Acad Sci USA,2006,103(7):2257-2261.
24、Krek,A.,Grun,D.,Poy,M.N.,Wolf,R.,Rosenberg,L.,Epstein,E.J.,et al.Combinatorial microRNA target predictions.Nat Genet,2005,37(5):495-500.
25、Bartel,D.P.MicroRNAs:genomics,biogenesis,mechanism,and function.Cell,2004,116(2):281-297.
26、Meister G,Landthaler M,Dorsett Y,Tuschl T.Sequence-specific inhibition of microRNA-and siRNA-induced RNA silencing.RNA,2004,10(3):544-550.
27、Esau C,Davis S,Murray SF,Yu XX,Pandey SK,Pear M et al.miR-122regulation of lipid metabolism revealed by in vivo antisense targeting.Cell Metab,2006,3(2):87-98.
28、Tsonis PA,Call MK,Grogg MW,Sartor MA,Taylor RR,Forge A,Fyffe R,Goldenberg R,Cowper-Sal-lari R,Tomlinson CR.MicroRNAs and regeneration:Let-7 members as potential regulators of dedifferentiation in lens and inner ear hair cell regeneration of the adult newt.Biochem Biophys Res Commun,2007,362(4):940-945.
29、Makarev E,Spence JR,Del Rio-Tsonis K,Tsonis PA.Identification of microRNAs and other small RNAs from the adult newt eye.Mol Vis,2006,15(12):1386-1391.
30、Ryan DG,Oliveira-Fernandes M,Lavker RM.MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity.Mol Vis,2006,17(12):1175-1184.
31、Frederikse PH,Donnelly R,Partyka LM.miRNA and Dicer in the mammalian lens:expression of brain-specific miRNAs in the lens.Histochem Cell Biol,2006,126(1):l-8.
32、Karah M,Peluso I,Marigo V,Banfi S.Identification and characterization of microRNAS expressed in the mouse eye.Invest Ophthalmol Vis Sci,2007,48(2):509-515.
33、Arora A,McKay GJ,Simpson DA.Prediction and verification of miRNA expression in human and rat retinas.Invest Ophthalmol Vis Sci,2007,48(9):3962-3967.
34、Xu S,Witmer PD,Lumayag S,Kovacs B,Valle D.MicroRNA (miRNA)transcriptome of mouse retina and identification of a sensory organ-specific miRNA cluster.J Biol Chem,2007,282(24):25053-25066.
35、Kuehbacher,A.et al.Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis.Circ.Res,2007,101(1):59-68.
36、Suarez,Y.et al.Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells.Circ.Res,2007,100(8):1164-1173.
37、Poliseno,L.et al.MicroRNAs modulate the angiogenic properties of HUVECs.Blood,2006,108(9):3068-3071.
38、Hua,Z.et al.MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia.PLoS ONE,2006,27(1):116.
39、Loscher CJ,Hokamp K,Kenna PF,Ivens AC,Humphries P,Palfi A,Farrar GJ.Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa.Genome Biol.2007,8(11):248.
40、Grishok A,Sharp PA.Negative regulation of nuclear divisions in Caenorhabditis elegans by retinoblastoma and RNA interference-related genes.Proc Natl Acad Sci USA.2005,29;102(48):17360-17365.
41、Worley LA,Long MD,Onken MD,Harbour JW.Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling.Melanoma Res.2008,18(3):184-190.
42、Silber J,Lim DA,Petritsch C.miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells.BMC Med.2008,24(6):14.
43、Venturini,L.et al.Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML)CD34+ cells.Blood,2007,109(10):4399-4405.
44、Bilen J,Liu N,Bonini NM.A new role for microRNA pathways:modulation of degeneration induced by pathogenic human disease proteins.Cell Cycle.2006,5(24):2835-2838.
45、Shen J,Yang X,Xie B,Chen Y,Swaim M,Hackett SF,Campochiaro PA.MicroRNAs regulate ocular neovascularization.Mol Ther.2008,16(7):1208-1216.
2.Esquela-KerscherA,Slack FJ.Oncomirs-microRNAs with a role in cancer.NatRev Cancer,2006,6 (4):259-269.
3.Slack FJ,Weidhaas JB.MicroRNAs as a potentialmagic bullet in cancer.FutOncol,2006,2 (1):73-82.
4.Makarev E,Spence JR,Del Rio-Tsonis K,Tsonis PA.Identification of microRNAs and other small RNAs from the adult newt eye.Mol Vis,2006,15(12):1386-1391.
5.Ryan DG,Oliveira-Fernandes M,Lavker RM.MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity.Mol Vis,2006,17(12):1175-1184.
6.Karah M,Peluso I,Marigo V,Banfi S.Identification and characterization of microRNAS expressed in the mouse eye.Invest Ophthalmol Vis Sci,2007,48(2):509-515.
7.Kuehbacher,A.et al.Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis.Circ.Res,2007,101 (1):59-68.
8.Suarez,Y.et al.Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells.Circ.Res,2007,100 (8):1164-1173.
9.Poliseno,L.et al.MicroRNAs modulate the angiogenic properties of HUVECs.Blood,2006,108 (9):3068-3071.
10.Hua,Z.et al.MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia.PLoS ONE,2006,27(1):116.
11.Meister G,Landthaler M,Dorsett Y,Tuschl T.Sequence-specific inhibition of microRNA-and siRNA-induced RNA silencing.RNA,2004,10(3):544-550.
12.Esau C,Davis S,Murray SF,Yu XX,Pandey SK,Pear M et al.miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting.Cell Metab,2006,3(2):87-98.
13.Pham I,Uchida T,Planes C,Ware LB,Kaner R,MatthayMA,et al.Hypoxiaup regulates V EGF expression in alveolr epithelial cells in vitro and in vivo[J].Am J Physiol Lung Cell Mol P hysiol 2002,283(5):1133-1142.
14.Takekoshi K,Isobe K,Yashiro T,Hara H,Ishii K,Kawakami Y,et al.Expression of vascular endothelial growth factor (VEGF)and its cognate receptors in human pheochromocytomas [J].Life Sci 2004,74(7):863-871.
15.Dawson DW,Volpert OV,Gillis P,et al.Pigment epithelium-derived factor:a potent inhibitor of angiogenesis.[J].Science 1999,285(5425):245-248.
16.Grossniklaus HE,Ling JX,Wallace TM,Dithmar S,Lawson DH,Cohen C,et al.Macroplage and retinal pigment epiyhelium expression of angiogenic cytokines in choroidal neovascularization.Mol Vis 2002,21(8):! 19-126.
1.曲冬懿,何守志.VEGF-B 及其受体 Flt-1在氪激光诱导的大鼠脉络膜新生血管中的表达.眼科新进展,2005,25(2):123-126.
2.曲冬懿何守志.血管生成素-2及其受体在脉络膜新生血管中的表达.眼科研究,2005,23(3):249-251.
3.赵世红,何守志.碱性成纤维细胞生长因子及其受体 FGFR1在脉络膜新生血管中的表达.眼科研究,2003,21(3):234-237.
4.史雪辉,何守志.转化生长因子β及其受体在实验性脉络膜新生血管中的表达及意义.眼科,2006,15(4):262-266.
5.史雪辉,何守志,陈学国.色素上皮衍生因子对氪激光诱导大鼠脉络膜新生血管的抑制作用.中国激光医学杂志,2006,15(2):74-78.
6.陈松,韩梅.老年性黄斑变性黄斑部脉络膜血循环研究[J].中华眼底病杂志2002;18(2):116-118.
7.Grunwald JE et al.Vascular endothelial growth factor and severity of nonproliferative diabetic retinopathy mediate retinal hemodynamics in vivo:a potential role for vascular endothelial growth factor in the progression of nonproliferative diabetic retinopathy.Invest Ophthalmol Vis Sci,1998;39(2):385.
8.Grossniklaus HE,Ling JX,Wallace TM,Dithmar S,Lawson DH,Cohen C,et al.Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization.Mol Vis.2002,21(8):119-126.
9.Bouck N.PEDF:antiangiogenic guideline of ocular function.Trends Mol Med,2002,8(7):330-334.
10.Holekamp NM,BouckN,Volpert O.Pigment epithelium-derived factor is deficient in the vitreous of patients with choroidal neovascularization due to age-related macular degeneration.Am J Ophthalmol,2002,134(2):220-227.
11.Duh EJ,Yang HS,Suzuma I,et al.Pigment epithelium derived factor supp resses ischemia induced retinal neovascularization and VEGF-induced migration and growth [J].Invest Ophthalmol Vis Sci,2002,43 (3):821-829.
12.Dawson DW,Volpert OV,Gillis P,et al.Pigment epithelium derived factor:a potent inhibitor of angiogensis[J].Science,1999,285(5425):245-248.
13.Tombran-Tink J,Shivaram SM,Chader GJ,et al.Expression,secretion,and age-related down regulation of pigment epithelium derived factor,a serpin with neurotrophic activity [J].J Neurosci,1995,15(7 Pt l):4992-5003.
14.Alberdi E,Aymerich MS,Becerra SP.Binding of pigment epithelium derived factor(PEDF)to retinoblastoma cells and cerebellar granule neurons.Evidence for a PEDF receptor[J].J Biol C hem,1999,274(44):31605-31612.
15.Kidner CA,Martienssen,RA.Macro effects of microRNAs in plants.Trends Genet,2003,19(1):13-16.
16.Kuehbacher,A.et al.Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis.Circ.Res,2007,101(1):59-68.
17.Suarez,Y.et al.Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells.Circ.Res,2007,100(8):1164-1173.
18.Poliseno,L.et al.MicroRNAs modulate the angiogenic properties of HUVECs.Blood,2006,108(9):3068-3071.
19.(a)Gao,X.,Gulari,E.,and Zhou,X.(2004)In situ synthesis of oligonucleotide microarrays.Biopolymers 73,579-596;(b)Zhu,Q.,Hong,A.,Sheng,N.,Zhang,X.,Jun,K.-Y.,Srivannavit,O.,Gulari,E.,Gao,X.,and Zhou,X.(2006)Microfluidic biochip for nucleic acid and protein analysis,in Methods Mol.Biol.Ed.Rampal,J.B.in press.
20.Bolstad,B.M.,Irizarry,R.A.,Astrandand,M.,Speed,T.P.A comparison of normalization methods for high density oligonucleotide array data based on variance and bias.Bioinformatics.2003,19(2),185-193.
21.Lee RC,Feinbaum RL,Ambros V.The C.elegans heteroch ronic gene lin-4 encodes small RNA with antisense complementarity to lin-14.Cell,1993,75(5):843-854.
22.ReinhartBJ,Slack FJ,BassonM,et al.The 21 nucletide let-7 RNA regulates developmental timing in caenorhabd it is elegans.Nature,2000,403(6772):901-906.
23.Carthew RW.Gene rgulation by microRNAs.Curr Opin GenetDev,2006,16(2):203-208.
24.Esquela-KerscherA,Slack FJ.Oncomirs-microRNAs with a role in cancer.Nat Rev Cancer,2006,6(4):259-269.
25.Slack FJ,Weidhaas JB.MicroRNAs as a potentialmagic bullet in cancer.FutureOncol,2006,2(1):73-82.
26.Ryan DG,Oliveira-Fernandes M,Lavker RM.MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity.Mol Vis,2006,17(12):1175-1184.
27.Frederikse PH,Donnelly R,Partyka LM.miRNA and Dicer in the mammalian lens:expression of brain-specific miRNAs in the lens.Histochem Cell Biol,2006,126(1):1-8.
28.Karah M,Peluso I,Marigo V,Banfi S.Identification and characterization of microRNAS expressed in the mouse eye.Invest Ophthalmol Vis Sci,2007,48(2):509-515.
29.Loscher CJ,Hokamp K,Kenna PF,Ivens AC,Humphries P,Palfi A,Farrar GJ.Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa.Genome Biol.2007,8(11):248.
30.Worley LA,Long MD,Onken MD,Harbour JW.Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling.Melanoma Res.2008,18(3):184-190.
31.Bilen J,Liu N,Bonini NM.A new role for microRNA pathways:modulation of degeneration induced by pathogenic human disease proteins.Cell Cycle.2006,5(24):2835-2838.
32.Kuehbacher,A.et al.Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis.Circ Res,2007,101(1):59-68.
33.Suarez,Y.et al.Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells.Circ Res,2007,100(8):1164-1173.
34.Pohseno,L.et al.MicroRNAs modulate the angiogenic properties of HUVECs.Blood,2006,108(9):3068-3071.
35.Ritu Kulshreshtha,Manuela Ferracin,Sylwia E,Wojcik,et al.A MicroRNA Signature of Hypoxia,Molecular and cellular biology,2007,27(5):1859-1867.
36.Shen J,Yang X,Xie B,Chen Y,Swaim M,Hackett SF,Campochiaro PA.MicroRNAs regulate ocular neovascularization.Mol Ther.2008,16(7):1208-1216.
37.Zhong Hual.a,Qing Lvl.a,WenbinYe.MiRNA-Directed Regulation of VEGF and Other Angiogenic Factors under Hypoxia,www.plosone.org,2006,Issue l,el16:l-13.
38.Chen JF,Mandel EM,Thomson JM,Wu Q,Callis TE,Hammond SM et al.The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.Nat Genet,2006;38(2):228-233.
39.Poliseno L.et al.MicroRNAs modulate the angiogenic properties of HUVECs.Blood,2006,108(9):3068-3071.
40.Roccaro AM,Sacco A,Chen C.microRNA expression in the biology,prognosis and therapy of Waldenstrom macroglobulinemia.Blood.2009,113(18):4391-4402.
41.Teng G,Papavasihou FN.Shhh! Silencing by microRNA-155.Philos Trans R Soc LondB Biol Sci.2009,12;364(1517):631-637.
42.Yang H,He L,Zhao J,Coppola D,Dalton WS,Cheng JQ.MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA.Mol Cell Biol.2008,28(22):6773-6784.
1、Kidner CA,Martienssen RA.Macro effects of microRNAs in plants.Trends Genet,2003,19(1):13-16.
2、Denlil AM,Tops BB,et al.Processing of primary microRNAs by the Microprocessor complex.Nature,2004,432(7014):231-235.
3、Bartel,DP.MicroRNAs:genomics,biogenesis,mechanism,and function.Cell,2004,116(2):281-297.
4、Chen PY,Meister G.microRNA-guided posttranscriptional generegulation.BiolChem,2005,386(12):1205-1218.
5、Liu J,Gao Y,et al.Effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation.World J Gastroenterol,2005,11(8):1161-1166.
6、Valencia-Sanchez M.A.,Liu J.,Hannon G.J.,Parker,R.Control of translation and mRNA degradation by miRNAs and siRNAs.Genes Dev,2006,20(5):515-524.
7、Esquela-KerscherA,Slack FJ.Oncomirs-microRNAs with a role in cancer.NatRev Cancer,2006,6(4):259-269.
8、Slack F J,Weidhaas JB.MicroRNAs as a potentialmagic bullet in cancer.FutOncol,2006,2(1):73-82.
9、Shingara J,Keiger K,Shelton J,Laosinchai-Wolf W,Powers P,Conrad R et al.An optimized isolation and labeling platform for accurate microRNA expression profiling.RNA,2005,11(9):1461-1470.
10、Lu J,Getz G,Miska EA,Alvarez-Saavedra E,Lamb J,Peck D et al.MicroRNA expression profiles classify human cancers.Nature,2005,435(7043):834-838.
11、Neely LA,Patel S,Garver J,Gallo M,Hackett M,McLaughlin S et al.A single-molecule method for the quantitation of microRNA gene expression.Nat Methods,2006,3(1):41^16.
12、Mattie MD,Benz CC,Bowers J,Sensinger K,Wong L,Scott GK et al.Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies.Mol Cancer,2006,19(5):24.
13、Schratt GM,Tuebing F,Nigh EA,Kane CG,Sabatini ME,Kiebler M et al.A brain-specific microRNA regulates dendritic spine development.Nature,2006,439(7074):283-289.
14、Chen JF,Mandel EM,Thomson JM,Wu Q,Callis TE,Hammond SM et al.The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.Nat Genet,2006,38(2):228-233.
15、Hwang HW,Mendell JT.MicroRNAs in cell proliferation,cell death and tumorigenesis.Br J Cancer,2006,94(6):776-780.
16、Chen CZ.MicroRNAs as oncogenes and tumor suppressors.N Engl J Med,2005,353(17):1768-1771.
17、Cimmino A,Calin GA,Fabbri M,Iorio MV,Ferracin M,Shimizu M et al.miR-15 and miR-16 induce apoptosis by targeting BCL2.Proc Natl Acad Sci USA,2005,102(39):13944-13949.
18、Johnson SM,Grosshans H,Shingara J,Byrom M,Jarvis R,Cheng A et al.RAS is regulated by the let-7 microRNA family.Cell,2005,120(5):635-647.
19、Hayashita Y,Osada H,Tatematsu Y,Yamada H,Yanagisawa K,Tomida S et al.A polycistronic microRNA cluster,miR-17-92,is overexpressed in human lung cancers and enhances cell proliferation.Cancer Res,2005,65(21):9628-9632.
20、Chan JA,Krichevsky AM,Kosik KS.MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells.Cancer Res,2005,65(14):6029-6033.
21、 Eis PS,Tam W,Sun L,Chadburn A,Li Z,Gomez MF et al.Accumulation of miR-155 and BIC RNA in human B cell lymphomas.Proc Natl Acad Sci USA,2005,102(10):3627-3632.
22、Calin GA,Ferracin M,Cimmino A,Di Leva G,Shimizu M,Wojcik SE et al.A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia.N Engl J Med,2005,353(17):1793-1801.
23、Volinia S,Calin GA,Liu CG,Ambs S,Cimmino A,Petrocca F et al.A microRNA expression signature of human solid tumors defines cancer gene targets.Proc Natl Acad Sci USA,2006,103(7):2257-2261.
24、Krek,A.,Grun,D.,Poy,M.N.,Wolf,R.,Rosenberg,L.,Epstein,E.J.,et al.Combinatorial microRNA target predictions.Nat Genet,2005,37(5):495-500.
25、Bartel,D.P.MicroRNAs:genomics,biogenesis,mechanism,and function.Cell,2004,116(2):281-297.
26、Meister G,Landthaler M,Dorsett Y,Tuschl T.Sequence-specific inhibition of microRNA-and siRNA-induced RNA silencing.RNA,2004,10(3):544-550.
27、Esau C,Davis S,Murray SF,Yu XX,Pandey SK,Pear M et al.miR-122regulation of lipid metabolism revealed by in vivo antisense targeting.Cell Metab,2006,3(2):87-98.
28、Tsonis PA,Call MK,Grogg MW,Sartor MA,Taylor RR,Forge A,Fyffe R,Goldenberg R,Cowper-Sal-lari R,Tomlinson CR.MicroRNAs and regeneration:Let-7 members as potential regulators of dedifferentiation in lens and inner ear hair cell regeneration of the adult newt.Biochem Biophys Res Commun,2007,362(4):940-945.
29、Makarev E,Spence JR,Del Rio-Tsonis K,Tsonis PA.Identification of microRNAs and other small RNAs from the adult newt eye.Mol Vis,2006,15(12):1386-1391.
30、Ryan DG,Oliveira-Fernandes M,Lavker RM.MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity.Mol Vis,2006,17(12):1175-1184.
31、Frederikse PH,Donnelly R,Partyka LM.miRNA and Dicer in the mammalian lens:expression of brain-specific miRNAs in the lens.Histochem Cell Biol,2006,126(1):l-8.
32、Karah M,Peluso I,Marigo V,Banfi S.Identification and characterization of microRNAS expressed in the mouse eye.Invest Ophthalmol Vis Sci,2007,48(2):509-515.
33、Arora A,McKay GJ,Simpson DA.Prediction and verification of miRNA expression in human and rat retinas.Invest Ophthalmol Vis Sci,2007,48(9):3962-3967.
34、Xu S,Witmer PD,Lumayag S,Kovacs B,Valle D.MicroRNA (miRNA)transcriptome of mouse retina and identification of a sensory organ-specific miRNA cluster.J Biol Chem,2007,282(24):25053-25066.
35、Kuehbacher,A.et al.Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis.Circ.Res,2007,101(1):59-68.
36、Suarez,Y.et al.Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells.Circ.Res,2007,100(8):1164-1173.
37、Poliseno,L.et al.MicroRNAs modulate the angiogenic properties of HUVECs.Blood,2006,108(9):3068-3071.
38、Hua,Z.et al.MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia.PLoS ONE,2006,27(1):116.
39、Loscher CJ,Hokamp K,Kenna PF,Ivens AC,Humphries P,Palfi A,Farrar GJ.Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa.Genome Biol.2007,8(11):248.
40、Grishok A,Sharp PA.Negative regulation of nuclear divisions in Caenorhabditis elegans by retinoblastoma and RNA interference-related genes.Proc Natl Acad Sci USA.2005,29;102(48):17360-17365.
41、Worley LA,Long MD,Onken MD,Harbour JW.Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling.Melanoma Res.2008,18(3):184-190.
42、Silber J,Lim DA,Petritsch C.miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells.BMC Med.2008,24(6):14.
43、Venturini,L.et al.Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML)CD34+ cells.Blood,2007,109(10):4399-4405.
44、Bilen J,Liu N,Bonini NM.A new role for microRNA pathways:modulation of degeneration induced by pathogenic human disease proteins.Cell Cycle.2006,5(24):2835-2838.
45、Shen J,Yang X,Xie B,Chen Y,Swaim M,Hackett SF,Campochiaro PA.MicroRNAs regulate ocular neovascularization.Mol Ther.2008,16(7):1208-1216.