SUMO化修饰影响NAC1在卵巢癌耐药中的作用

Ovarian cancer is a common gynecological malignancy in female patients around the world. NAC1 expresses highly in ovarian cancer and regulates cancer cells chemotherapy resistance through kinds of mechanisms.Our previous research work revealed that NAC1 was a SUMO target, but what functions of NAC1 affected by SUMO are still unknown. This work is going to find the exact SUMO modification sites through site mutating and SUMOylating. By comparing the localization, protein stability, sensitivity of ovarian cancer cells to chemotherapy drugs and changes of gene expression invovled in known NAC1-regulated pathways after SUMO sites mutation of NAC1, we want to know how SUMO regulates NAC1 in ovarian cancer cells. Further more, by testing ovarian cancer cells apoptosis-related markers after being treated with chemotherapy drugs, we want to detect if SUMOylated NAC1 regulates Parkin and how sensitive are ovarian cancer cells to chemotherapy drugs by this regulation. From the perspective of SUMOylation, this work will provide novel mechanisms on NAC1 in ovarian cancer cells. By detecting the functions of NAC1 regulated by SUMO, our work will provide the theory basis for therapy.

卵巢癌是女性生殖系统三大恶性肿瘤之一。NAC1在卵巢癌中高表达并通过多种机制调控卵巢癌耐药。本课题组前期工作中发现NAC1是SUMO的底物，但SUMO化修饰影响哪些NAC1的生物学功能尚不清楚。本课题拟通过点突变及细胞内外SUMO化修饰检测，明确NAC1的具体SUMO化修饰位点；通过检测SUMO化修饰位点突变后的NAC1在细胞内定位、蛋白稳定性、卵巢癌细胞对化疗药物的敏感性和对已知耐药通路基因调控的变化，来揭示SUMO对NAC1功能的影响；进一步通过对卵巢癌细胞经化疗药物处理后细胞凋亡相关检测，探讨NAC1及其SUMO化修饰对Parkin的调控影响卵巢癌细胞对化疗药物的敏感性。此研究从蛋白质翻译后修饰角度出发，为认识NAC1在卵巢癌中的作用提供新的机理；并通过探讨SUMO化修饰影响NAC1在卵巢癌细中的作用，为临床治疗提供重要的理论依据。

卵巢癌是女性生殖系统三大恶性肿瘤之一。NAC1在卵巢癌中高表达并通过多种机制调控卵巢癌耐药。本课题组前期工作中发现NAC1是SUMO的底物，但SUMO化修饰影响哪些NAC1的生物学功能尚不清楚。本课题拟通过点突变及细胞内外SUMO化修饰检测，明确NAC1的具体SUMO化修饰位点；通过检测SUMO化修饰位点突变后的NAC1在细胞内定位、蛋白稳定性、卵巢癌细胞对化疗药物的敏感性和对已知耐药通路基因调控的变化，来揭示SUMO对NAC1功能的影响；进一步通过对卵巢癌细胞经化疗药物处理后细胞凋亡相关检测，探讨NAC1及其SUMO化修饰对Parkin的调控影响卵巢癌细胞对化疗药物的敏感性。此研究从蛋白质翻译后修饰角度出发，为认识NAC1在卵巢癌中的作用提供新的机理；并通过探讨SUMO化修饰影响NAC1在卵巢癌细中的作用，为临床治疗提供重要的理论依据。