miR-28-TXNL1-XRCC1轴在顺铂诱导胃癌细胞凋亡中的作用及分子机制研究

顺铂可以诱导DNA损伤和细胞凋亡，临床上利用这一特性用于多种肿瘤包括胃癌的治疗，但仍然存在肿瘤细胞对顺铂化疗不敏感和顺铂的过度治疗引发的毒副反应等问题，所以深入研究顺铂诱导DNA损伤和细胞凋亡的机制对于制定科学的肿瘤防治策略，最终实现个体化治疗具有非常重要的意义。本项目在前期研究发现XRCC1参与顺铂诱导DNA损伤和细胞凋亡的基础上，拟通过细胞和动物模型，并结合人群研究，利用分子细胞生物学相关技术和分子流行病学相关方法进一步探讨miR-28-TXNL1-XRCC1轴通过平衡和转换DNA修复和细胞凋亡相关信号网络调控顺铂诱导细胞凋亡的分子机制和以这三个分子为轴心的多分子作为联合预测胃癌患者顺铂化疗疗效的分子标志及治疗靶标的意义，为提出胃癌防治新思路提供理论依据。

Cisplatin can induce DNA damage and apoptosis, which was employed to treat a wide array of solid malignancies including gastric cancer. However, there are many issues such as the tumor cells are no response to cisplatin and the patients are unnessesarily treated and only get severe side effects. Therefore, it is urgent to explore the mechanism involved in cisplatin-induced DNA damage and apoptosis, which will be important to formulate the stratege for personalizing gastric cancer treatment. Based on our previous study indicated that XRCC1 plays a key role in cisplatin-induced DNA damage and apoptosis, we will use cellular, animal models and cohort study with molecular and cellular biological skills and epidemiology methods to identify the mechanisms of miR-28-TXNL1-XRCC1 axis in regulating cisplatin-induced apoptosis via balancing and switching the signaling pathways between DNA repair and apoptosis, and indicate the significance of miR-28-TXNL1-XRCC1 as the biomarkers and treatment targets to predict the effect of cisplatin in chemotherapy, which will provide new strategy for preventing and treating gastric cancer.