化疗耐药或复发是造成卵巢癌预后不良的主要原因。国外报道 Dicer1 低表达和卵巢癌的预后差相关，具体机制不明。我们前期实验结果首次发现Dicer1低表达能够促进卵巢癌线粒体生物合成及功能的活化，同时提高ROS清除能力导致顺铂耐药，且该过程和PGC-1α活化相关。因此在本项目中，我们拟从三个方面验证并完善这个假说，并且根据该假说探索新的联合治疗方案。即：1. 揭示Dicer1通过microRNAs(miRs)调控PGC-1α表达的具体机制；2. 从大样本卵巢癌临床标本中进一步验证Dicer1、miRs、PGC-1α之间的关系，并分析其和卵巢癌患者预后之间的关系；3. 针对我们提出的这个机制，体内外探索新的联合治疗方案的疗效：Dicer1高表达者给予化疗药物联合ROS诱导剂，而对Dicer1低表达者给予化疗药物联合线粒体氧化磷酸化抑制剂。

Cancer chemotherapy resistance or recurrence are the main causes of poor prognosis of ovarian cancer. It has been reported that low Dicer1 expression was associated with poor prognosis of ovarian cancer, but, the detailed mechanism behind is unknown. Our preliminary results for the first time indicated that low Dicer1 expression increased mitochondria biogenesis and oxidative phosphorylation function activation, enhancing reactive oxygen species (ROS) detoxification capacities, resulting in resistance to Cisplatin. Moreover, we found that this process was accomplished with PGC-1α activation. Therefore, in this project, we intend to verify our findings and to improve this hypothesis in three aspects. Futhermore, we want to explore new combination therapy according to our hypothesis. 1). to reveal the detailed mechanism how Dicer1 regulates the PGC-1α expression through microRNAs (miRs); 2). to further verify the relationship among Dicer1, miRs and PGC-1α in a large samples of ovarian cancer, to explore the correlation between the expression of Dicer1, miRs or PGC-1α and the prognosis of ovarian cancer; 3). to explore the therapeutic effects of new targeted combination therapies in vitro and in vivo based on our hypothesis: using chemotherapy combining with ROS inducer for high Dicer1 expression cells, and using chemotherapy combining with mitochondrial oxidative phosphorylation inhibitors for low Dicer1 expression cells.