lincRNA-CDM竞争结合let-7上调Cyclin D1促进膀胱癌演进的机制研究

最近研究表明长链基因间非编码RNA（lincRNAs）的异常表达在肿瘤中起着癌基因/抑癌基因的作用。我们预实验发现lincRNA-CDM在膀胱癌组织中过表达，下调lincRNA-CDM表达能使膀胱癌细胞增殖、迁移及侵袭能力下降；细胞阻滞在G1期，且周期蛋白cyclin D1 表达明显下调。生物信息学分析提示lincRNA-CDM与 cyclin D1 3'-UTR均有多个miRNA let-7结合位点。由此，我们提出lincRNA-CDM在膀胱癌中的作用新机制，即：lincRNA-CDM通过竞争性结合let-7，减少了let-7对Cycin D1的抑制作用，从而促进膀胱癌演进和转移。本研究拟在体内外实验水平研究lincRNA-CDM的功能，获得lincRNA-CDM通过竞争性结合let-7，上调CCND1表达的可靠依据，分析lincRNA-CDM与膀胱癌临床病理指标的关系，指导临床实践。

Recent studies revealed that deregulation of long intergenic noncoding RNA(lincRNAs) play important role in cancinogenesis, acting as oncogenes or tumor suppressor genes.Our previous research showed that lincRNA-CDM is overexpressed in bladder cancer tissue. Knock down of lincRNA-CDM in bladder cancer cells decelerated biological activity of proliferation, motility and invasiveness,and tumor cells were arrested at G0/G1.Further Study showed knock down of lincRNA-CDM up-regulating Cyclin D1 expression. Bioinformatic analysis showed that lincRNA-CDM and Cyclin D1 3'-untranslated region share several let-7 binding sites. Therefore,we propose the new mechanism that lincRNA-CDM modulates cyclin D1 expression through binding let-7 competitively thus decreases the inhibitory effect of let-7 on cyclin D1 and promotes bladder cancer progression. This study is aimed at exploring function and mechanism of lincRNA-CDM in vitro and in vivo, providing theoretical evidence for bladder cancer targeting therapy.