PKM2促进子宫内膜癌细胞增殖的作用及机制研究

The mechanism of PKM2 on promoting the proliferation of endometrial cancer cells

目的研究PKM2在子宫内膜癌细胞增殖中的作用及相关机制。方法采用TCGA数据库及瑞金RNA表达谱数据库分析PKM2在子宫内膜癌和正常内膜中的表达差异。实时定量PCR、免疫印迹法及免疫组化法检测PKM2在内膜癌细胞株及正常内膜组织、内膜癌组织中的表达。慢病毒敲低PKM2表达,检测内膜癌细胞功能变化。结果PKM2在内膜癌组织中表达上调,其表达上调与组织学分级及不良预后相关。在内膜癌细胞株中下调PKM2可显著抑制细胞增殖。高表达的PKM2可增加缺氧诱导因子1α(HIF-1α)募集,激活NF-κB信号通路发挥促癌作用。结论PKM2可能作为内膜癌患者治疗的潜在靶点。

Objective:To explore the mechanism of PKM2 on promoting the proliferation of endometrial cancer cells.Methods:TCGA database and Ruijin cohort were used to analyze the PKM2 expression in EC tissues and normal tissues.Quantitative real-time PCR,Western blot and immunohistochemistry(IHC)were performed to detect the PKM2 expression in EC tissues and cells.The functional changes of EC cells and potential mechanism were explored after PKM2 silencing.Results:PKM2 was up-regulated in EC tissues compared with normal controls associated with tumor grade and poor prognosis.PKM2 knockdown inhibited EC cell proliferation in vitro.Mechanistically,highly expressed PKM2 up-regulated hypoxia inducible factor 1α(HIF-1α)accumulation and activated NF-κB pathway signaling.Conclusion:PKM2 may serve as a prognostic predictor and a treatment target in EC patients.