miR-17-92基因簇在细胞衰老过程中的转录调控机制

项目名称： miR-17-92基因簇在细胞衰老过程中的转录调控机制

项目编号： No.31201038

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 王苗

作者单位： 杭州师范大学

项目金额： 23万元

中文摘要： microRNA是一类进化上保守的非编码RNA，在转录后水平抑制蛋白编码基因的表达。microRNA代表一个新层次上的基因表达调控方式，通过调控基因表达参与发育、分化、衰老及癌变等许多重要生物学过程。miR-17-92基因簇是第一个被鉴定的具有癌基因作用的microRNA基因簇，命名为oncomir-1，在多种肿瘤组织中过表达。 我们前期工作发现miR-17-92基因簇的成员miR-17-5p和miR-20a在细胞衰老过程中表达显著下调，并证明miR-17-5p和miR-20a通过抑制E2F1基因表达参与细胞衰老的调节。有报道显示miR-17-92基因簇中的miR-17-5p，miR-19b和miR-20a在人的四种细胞衰老模型和三种组织衰老模型中表达显著下调，说明miR-17-92基因簇在细胞和组织衰老中起重要作用。本项目拟研究miR-17-92基因簇在细胞衰老过程中转录调节机制。

中文关键词： 细胞衰老；miR-17-92基因簇；转录调控；；

英文摘要： microRNAs are recently discovered class of small non-coding RNA species that regulate gene expression at the post-transcriptional level. microRNAs that represented a novel regulatory mechanism in gene expression play fundamental roles in a broad spectrum of biological activities, including development, differentiation, cell death and oncogenesis. miR-17-92 cluster was the first microRNA cluster identified with oncogenic potential and was therefore termed as oncomir-1, which frequently altered or dysregulated in various human cancers. We have previously identified two members of the miR-17-92 cluster microRNAs miR-17-5p and miR-20a down-regulated in senescent cells. We further showed that miR-17-5p and miR-20a involved in the cellular senescence by targeting the cell cycle regulator E2F1. Recent studies demonstrated that the members of miR-17-92 cluster miR-17-5p, miR-19b and miR-20a are down regulated in human aging including four cell types of cellular senescence model and three human aging tissues, suggesting that miR-17-92 cluster play important roles in cellular and organismal aging. By using bioinformatics and chip-seq experimental database analysis, we found that the promoter region of miR-17-92 cluster has a large CpG island, multiple H3K4me3, H3K9Ac sites and conserved transcription factor binding sites

英文关键词： cellular senescence；miR-17-92 cluster；transcriptional regulation；；