GDF15/miR497/CDC25A通路调控G1/S转化介导卵巢癌增殖的机制研究.........

上皮性卵巢癌是死亡率最高的妇科肿瘤，目前仍缺乏有效的分子靶向药物。我们前期工作证实生长分化因子15(GDF15)表达与卵巢癌患者病程进展、不良预后有关；GDF15表达下降显著抑制卵巢癌细胞增殖，同时细胞S期比例显著降低。miR-497是miR芯片筛选获得的受GDF15调控的差异miR分子，预实验提示卵巢癌细胞存在GDF15/miR-497/CDC25A通路，可能通过促进G1/S转化导致卵巢癌细胞恶性增殖，具体机制尚不明确。本课题将综合利用生物信息学分析、荧光素酶报告基因系统、ChIP、EMSA等技术验证GDF15/miR-497/CDC25A通路，并用MTT、细胞周期、BrdU ELISA、Cyclin E/CDK2体外激酶检测等系统研究GDF15/miR-497/CDC25A通路在卵巢癌细胞恶性增殖和G1/S转化中发挥的作用及调控机制。本课题将为卵巢癌的早期诊断和有效防治提供新的分子靶标

Epithelial ovarian cancer (EOC) is one of the most common malignant tumors with high incidence and mortality. It is still lack of specific molecular targeted anti-tumor agents for EOC patients. Our previous study showed that high GDF15 levels were obviously related with progression and poor survival in EOC patients. Decreased GDF15 expression obviously reduced the proliferation and the percent of S stage of ovarian cancer cells. By using microRNA chip assay we found that miR-497 was distinctly regulated by GDF15 gene, and was involved in the regulation of cell cycle in EOC cells. Our previous study suggested that there was GDF15/miR-497/CDC25A pathway related with G1/S transition in cell cycle of EOC cells. The mechanism of GDF15/miR-497/CDC25A pathway is still unknown. Based on our previous study, we will systematically investigate the role of GDF15/miR-497/CDC25A pathway in EOC cells and explore the function and regulation mechanism of GDF15/miR-497/CDC25A pathway in G1/S transition of EOC cells by using several biology technologies such as bioinformatics analysis, luciferase reporter system,ChIP,EMSA and so on. Our study would provide new potential drug targets for EOC patients.