项目名称: miR-320通过调控Mcl-1对宫颈癌细胞凋亡的作用和机制研究
项目编号: No.81202043
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2
项目作者: 张婷
作者单位: 南京医科大学
项目金额: 23万元
中文摘要: 宫颈癌是女性最常见的恶性肿瘤之一。细胞凋亡调控异常与肿瘤发生密切相关。我们前期研究发现抗凋亡蛋白Mcl-1在宫颈癌显著高表达,其表达水平与宫颈癌病理分级、肿瘤直径、淋巴结转移及患者预后密切相关。生物信息学分析提示Mcl-1是miR-320调控的靶基因,预实验发现宫颈癌miR-320表达显著下调。因此,我们推测miR-320可能通过调控Mcl-1参与宫颈癌发病机制。然而,目前关于miR-320对Mcl-1的调控作用和机制的研究尚属空白。本研究拟采用荧光素酶报告基因技术验证miR-320与Mcl-1靶向关系;在人宫颈癌细胞水平,明确miR-320对Mcl-1的调控机制及对细胞凋亡的影响,探讨Mcl-1介导宫颈癌细胞抗凋亡途径;在体水平进一步验证miR-320通过调控Mcl-1对宫颈癌细胞凋亡的作用与机制。本研究具有创新性,可为宫颈癌防治提供新的理论依据,具有重要的理论意义和临床应用价值。
中文关键词: miR-320;Mcl-1;宫颈癌;凋亡;
英文摘要: Cervical cancer is one of the most common malignancy in women. Abnormal regulation of apoptosis is closely related with tumorigenesis. Our preliminary findings showed that the expression of anti-apoptotic protein Mcl-1 was significantly higher in cervical cancer tissue when compared with corresponding normal tissue, and Mcl-1 expression profile was significantly associated with the pathological grade, tumor size, lymph node metastasis and prognosis. Bioinformatics analysis indicated that Mcl-1 is the target gene of miR-320, preliminary experiment found that miR-320 expression was significantly reduced in cervical cancer. So, we speculate that miR-320 may involved in the pathogenesis of cervical cancer via its regulation on Mcl-1. However, until now there is no a report about the regulation effect and mechanism of miR-320 on Mcl-1.In this study, we will firstly validate the target regulation of miR-320 on Mcl-1 by luciferase reporter genes assay; secondly, we will investigate the regulation mechanism of miR-320 on Mcl-1 and the effect on apoptosis of human cervical cancer cells, then explore the anti-apoptosis pathways which was mediated by Mcl-1. Finally, we will verify the effect and mechanism of miR-320 on apoptosis of cervical cancer cells via its regulation on Mcl-1 in vivo. This study is innovative and will
英文关键词: miR-320;Mcl-1;cervcial cancer;apoptosis;