miR-519d在肿瘤细胞周期调控中的作用及其分子机制研究

项目名称： miR-519d在肿瘤细胞周期调控中的作用及其分子机制研究

项目编号： No.81201565

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： 周珏宇

作者单位： 南方医科大学

项目金额： 23万元

中文摘要： microRNAs介导的细胞周期调控与肿瘤发生密切相关。前期的研究中，我们利用细胞同步化和miRNAs芯片技术对不同细胞周期时相的HeLa细胞的miRNAs表达谱进行了分析，证明了miR-519d等25种miRNAs的表达具有周期依赖性。进一步研究表明miR-519d在HeLa细胞内可能通过靶向p21和E2F1发挥癌基因的作用。然而，目前有关miR-519d在肿瘤发生中的作用及其机制仍存在一些争议。为此，本课题拟采用细胞同步化和Northern blot检测技术，以time-course的方法分析miR-519d在肝癌、胃癌等8种不同肿瘤细胞中的表达情况，运用细胞同步化和过表达/敲减实验明确其在肿瘤细胞周期调控中的确切作用，通过生物信息学分析与实验验证相结合的方法鉴定miR-519d的靶基因，并揭示其与靶基因间的相互关系，最终阐明miR-519d调控肿瘤细胞周期的分子机制。

中文关键词： 宫颈癌；微小RNA；细胞周期；转移；

英文摘要： Recent studies have identi?ed speci?c microRNAs that regulate the cell cycle and have documented that the loss or gain of miRNA-mediated cell-cycle control contributes to malignancy. MiRNAs regulate classic cell-cycle control pathways by directly targeting proteins such as E2F transcription factors, cyclin-dependent kinases (Cdks), cyclins and Cdk inhibitors. If miRNAs control the highly orchestrated patterns of gene expression that occur during cell cycle progression, it seems likely that miRNAs themselves might be subject to cell-cycle dependent regulation. Thus, it is hypothesized that expression of specific miRNAs oscillates orderly along with cell cycle progression. However, the oscillated expression patterns of many candidate miRNAs have yet to be determined. Our previous study described the miRNA expression profiling in double-thymidine synchronized HeLa cells as cell cycle progresses and suggested that twenty-five miRNAs, such as miR-519d, exhibit characteristic cell cycle stage-specific oscillations in HeLa cells. We also provided evidence that miR-519d gain of function promotes growth of HeLa cell by controlling cell cycle progression, whereas loss of function reverses this phenotype. Further study confirmed that p21 and E2F1 are direct targets of miR-519d. Although the function and mechanism of miR-51

英文关键词： cervical cancer；microRNA；cell cycle；metastasis；