皮膚中mirna研究綜述

1、microRNAs the DNA hidden treasure,Guo sen2012/2/28,A Simplified History of Life on Earth,,,,,,Mattick (2004) Nature Reviews Genetics 5: 316-323.,Ratio of Non-Protein-Coding DNA to Total Genomic DNA During Evolution,,Ho

2、mo sapiensRatio>95%,Mattick (2004) Nature Reviews Genetics 5: 316-323.,non-protein-coding RNAs represent a fundamental advance in the genetic operating system of higher organisms,Mattick (2004) Nature Reviews Genetic

3、s 5: 316-323.,Non-protein-coding RNA,rRNAtRNAsmall nuclear(sn) RNAsmall nucleolar (sno) RNAsmicro (mi) RNAssome of the lesser-known RNAs such as vault RNAs, rasi-RNAs and piRNAs,M Yeung (2007) Retrovirology4: 74,Lee

4、, R. C., Feinbaum, R. L. & Ambros, V. Cell 75, 843–854 (1993).Wightman, B., Ha, I. & Ruvkun, G. Cell 75, 855–862 (1993).,A small RNA （cel-lin-4）was identified which negatively regulate lin-14 expression post-

5、transcriptionally,Discovery of MiRNA,What is MiRNA,miRNAs are non-coding, single-stranded RNAs of ~22 nucleotidesmiRNAs are a large family of gene regulatorsmiRNAs suppress the expression of their target genes by sup

6、pressing the translation of target mRNAs,Where is MiRNA,,Intronic miRNAs often in antisense directionExonic miRNAs - non-coding (or in alternatively spliced exons),Zhao Y, Srivastava (2007)D, TIBS 32:189,,How does MiRN

7、A Work,miRNA-associated, multiprotein RNA induced-silencing complex (miRISC),,perfect complementaritycommonly found in plants,imperfect complementary,Annu. Rev. (2007)Cell Dev.Biol..23:175-205,miRNAs Inhibit Translation

8、 by Inducing Ribosome Drop-Off,,Petersen et al. (2006) Molecular Cell 21: 533-542.,The biogenesis of microRNAs,The biogenesis of microRNAs,Role of miRNA in gene regulation,miRNAs usually bind to their targets with incomp

9、lete complementaritya single miRNA might bind to as many as 200 gene targets and that these targets can be diverse in their functionmiRNAs potentially control the expression of about one-third of human mRNAs and have

10、 a broad influence over several diverse genetic pathways,MiRNAs and Skin disease,R Yi, et al. (2006)Nat Genet.;38(3):356-62.,miRNAs and skin morphogenesis,Phenotypic and morphological alterations accompanied in Dicer1 co

11、nditional null skin.,miRNAs and skin morphogenesis,The skin-speci?c miR-203 was recently linked to skin Morphogenesis. miR-203 represses p63 expression, an important factor in epidermal cell proliferation and differentia

12、tion,R Yi. (2010) Cell Death Differ 17: 229-235.,miRNAs and wound healing,Inflammatory:miR-140 has been shown to have a modulating effect on zebrafish platelet-derived growth factor(PDGF) receptor a,JK Eberhart. (2008) N

13、ature genetics 40(3): 290–298.,,,miRNAs and psoriasis,miR-203 was the ?rst miRNA found to be signi?cantly overexpressed in psoriasis patients,miR-203,,,SOCS-3,,,STAT-3,,E Sonkoly. (2007) PLoS One: 610.,Other miRNAs linke

14、d to psoriasis progression are miR-146a and miR-125b, which indirectly or directly regulate TNF-a expression,TNF-a,,miR-125b,,,miRNAs and psoriasis,Tili E. (2007) Journal of immunol;179: 5082-5089.,miRNAs and Melanoma,mi

15、R-182 enhances melanoma oncogenic behavior in vitro and in vivo,MF Segura. (2009) PNAS;106: 1814-1819.,,,expression of mature miR-137 in melanoma cell lines down-regulates MITF expression,miRNAs and Melanoma,,,,,LT Bemis

16、. (2008) Cancer research;68: 1362-1368.,miR-221, miR-222 and Let-7 plays a role in melanoma development and progression, as its predicted targets include a series of cancer-promoting molecules,miRNAs and Melanoma,M Sand.

17、 (2009) Journal of Dermatological Science; 53: 169-175.,,,Table . Expression profile and function of melanoma-associated miRNAs,miRNAs and skin disease– A Summary,miRNAs are misexpressed in skin disease and are therefore

18、 excellent diagnostic/prognostic markers in skin diseaseSome miRNAs e.g. mir-182, can cause melanoma and oncogenic miRNAs may be therapeutic targets in skin cancer MicroRNAs could augment current skin disease therapi