STON2/MUC1通路调控卵巢癌类干细胞干性特征的机制研究

肿瘤干细胞具有自我更新和无限增殖能力，并对外界理化因子的杀伤作用不敏感，被认为是癌症复发的原因之一，但其机制迄今尚不明确。我们通过定量蛋白质组学发现，STON2在3AO卵巢癌类干细胞的表达显著降低，且在低分化卵巢癌组织中表达明显低于中、中高分化卵巢癌组织，下调STON2表达能促进卵巢癌类干细胞干性活性，同时MUC1表达升高。本项目在已有工作基础上拟采用无血清悬浮培养、基因调控等手段观察调控STON2对卵巢癌类干细胞干性特征的影响，并通过RNA-seq，信息学分析、免疫共沉淀、免疫荧光共定位、反向调控等技术证实干性相关分子MUC1直接参与STON2对干性的调控，最后利用CRISPR/ Cas9 技术、动物模型和临床标本验证STON2的功能，从而阐明STON2调控卵巢癌类干细胞干性水平的分子机理，并揭示靶向调控STON2具有的潜在应用价值，为卵巢癌治疗提供新的科学证据。

Cancer stem cells possess the ability of self-renewal, unlimited proliferation，and non-sensitivity to physical and chemical factors, which is regarded to be a cause of ovarian cancer recurrence, but the mechanism is currently unclear. We found that the expression of STON2 was significantly lower in ovarian cancer-stem like cells by LC-MS/MS-based label free quantitative proteomics approach and Western Blot validation. And its expression in low differentiated ovarian cancer tissue is lower than in the middle and medium high differentiated ovarian cancer tissue. Our previous primary study showed that a facilitation of cancer stem-like cells properties by STON2 knock-down, with MUC1 high expression. In this study proposal, we plan to observe the effect of regulating STON2 expression on the ovarian cancer stem-like cells properties by serum-free culture and gene modulation. To identify that MUC1 participates directly in the process of STON2 mediating the regulation of the ovarian cancer stem-like cells properties by RNA-seq, IP, Immunofluorescence localization, and gene modulation. Finally, To verify the function of STON2 in ovarian cancer by CRISPR/Cas9, animal models and clinical samples. The aim of our study is to expound a novel mechanism that STON2 regulating the ovarian cancer stem-like cells properties and find out a potential strategy for ovarian cancer therapy.