RAS诱导miR-134调节人卵巢癌细胞增殖和迁移的作用机制

项目名称： RAS诱导miR-134调节人卵巢癌细胞增殖和迁移的作用机制

项目编号： No.81201589

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 吴建民

作者单位： 温州医科大学

项目金额： 23万元

中文摘要： RAS在信号转导、细胞增殖、恶性转化及肿瘤转移等方面起着极其重要的作用。约30%的恶性肿瘤中存在RAS突变。通过比较卵巢癌细胞株T29H（稳定转染癌基因H-RASv12）和T29的miRNA表达谱，我们发现H-RASv12明显诱导miR-134的表达；瞬时转染miR-134影响细胞的增殖和迁移能力；生物信息学预测并初步确认了PPP1R7，MYPT1和PHLPP2为miR-134的候选靶基因。本项目拟在此基础上深入研究H-RASv12对miR-134的调节，研究miR-134及其候选靶基因PPP1R7，MYPT1和PHLPP2对细胞增殖和迁移的影响，以阐明H-RASv12调节miR-134及其靶基因，诱导细胞增殖和迁移的分子机制；并应用临床卵巢癌标本研究H-RAS，H-RASv12与miR-134及其靶基因的相关性，深入研究RAS信号通路的致癌机理，为寻找抗肿瘤药物的新靶点提供理论依据。

中文关键词： miR-134；肿瘤发生；卵巢癌；MICA/B；肿瘤免疫

英文摘要： RAS has long been known to play a significant role in signal transduction，cell proliferation, tumor formation and metastasis. RAS mutations are found in approximately 30% human cancer. After comparing the miRNA expression between T29 (human ovarian epithelial cell immortalized with SV40T/t antigens and the human catalytic subunit of telomerase) and T29H (T29 transformed with an additional oncogenic H-RASv12) cell lines, we found that the expression of miR-134 was induced obviously by H-RASv12. Over-expression or inhibition of miR-134 significantly affected cell proliferation and migration. Bioinformatics prediction and Dual-luciferase assay preliminary validated that PPP1R7, MYPT1 and PHLPP2 were the candidate targets of miR-134. In this project, based on the results above, further studies will be performed, including: 1) identifying the signaling pathway by which H-RASv12 regulates the expression of miR-134; 2) determining the effects of miR-134 and its candidate targets (PPP1R7，MYPT1 and PHLPP2) on cell proliferation and migration; 3) clarifying the molecular mechanism that H-RASv12 regulates the expression of miR-134 and target genes, and eventually cell proliferation and migration; 4) performing the correlation analysis between the expression of H-RAS, H-RASv12, miR-134 and target genes in ovarian cancer spe

英文关键词： miR-134；Tumorigenesis；Ovarian cancer；MICA/B；Tumor immun