miR-193a-3p调控的长非编码RNA在膀胱癌多药耐受的作用和机制研究

项目名称： miR-193a-3p调控的长非编码RNA在膀胱癌多药耐受的作用和机制研究

项目编号： No.81472638

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 朱景德

作者单位： 安徽医科大学

项目金额： 80万元

中文摘要： 多药耐受是临床肿瘤化疗低效的根本原因，也是肿瘤的基础和转化医学研究的重要内容之一。我们前期工作表明受甲基化状态调控的miR-193a-3p通过下调PLAU，HIC2及SRSF2的表达，影响多个信号传导通路的活性来促进肝癌和膀胱癌的肿瘤生长和化疗耐受。长非编码RNA（LncRNA）以多种作用机制调控基因的表达，与蛋白编码基因类似，LncRNA的表达可在转录后水平受到miR的负调。通过LncRNA比较组学分析，发现6个（生物信息学预期的）可能受miR-193a-3p的调控LncRNA基因。其中lnc-SMAD3-1，lnc-FAM54B-1和lnc-AKIP1-3基因的表达得到qRT-PCR分析的肯定。为更深入的机制理解，我们将从这3个LncRNA基因的视角，开展分子、细胞和裸鼠移植瘤模型水平上的系统研究。

中文关键词： C13_膀胱肿瘤；DNA甲基化；长非编码RNA；化疗耐受；miR-193a-3p

英文摘要： 。The multidrug resistance prevencts curative cancer chemotherapy and demands an intensive investigation. Our previous studies have shown that the DNA methylation regulated miR-193a-3p represses the expression of the following three genes：SRSF2, PLAU and HIC2, affects multiple signaling pathways and promotes both the in vivo tumor growth and multi-drug chemo-resistance of both liver and bladder cancer. LncRNA is a loosely defined group of the non-coding RNAs with a diverse but crucial role in various biological and pathological conditions, including the multi-chemoresistance of cancer. Similar to the protein coding gene, its expression is under the negative regulation of miR, in addition to the transcription regulation. Via a comparative LncRNA expression profiling of a multi-chemosensitive (5637) and a resistant (H-bc) cell lines, several dozens of the differentially expressed LncRNA have been identified. Among six bioinformatically predicted miR-193a-3p's targetsm express in a negative pattern of the miR-193a-3p,the expected expression pattern of lnc-SMAD3-1，lnc-FAM54B-1 and lnc-AKIP1-3 was confirmed by qRT-PCR. For the novel mechanistic insights, we will perform a systematic study of this three LncRNAs at the molecular, cellular and the tumor/xenograft/nude mice levels, in the context of the multi-chemoresistance of bladder cancer..

英文关键词： Bladder cancer;DNA methylation;LncRNA;Chemoresistance;miR-193a-3p