PKM2抑制Hippo信号通路促进肝癌细胞增殖和侵袭迁移能力
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淮安市科技计划项目(HAB2017040);国家自然科学基金青年科学基金(81400650)


PKM2 promotes hepatocellular carcinoma cell proliferation,invasion and migration by decreasing Hippo signaling pathway
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    摘要:

    目的:探讨PKM2对肝癌细胞增殖和侵袭迁移能力的影响及其机制。方法:定量PCR、Western blot和免疫组化检测肝癌组织及肝癌细胞系(HepG2、Hep3B、Huh7和SMMC-7721)PKM2的表达;采用小干扰RNA(siRNA)抑制肝癌细胞PKM2表达,分析其对肝癌细胞增殖、侵袭和迁移的影响,并研究PKM2 siRNA对Hippo信号通路的影响。结果:定量PCR、Western blot和免疫组化显示PKM2在肝癌组织表达较癌旁组织表达明显升高,在肝癌细胞较肝细胞(L02)中表达明显升高;PKM2 siRNA可有效抑制肝癌细胞增殖、侵袭和迁移,进一步证实肝癌细胞中Hippo信号通路被抑制,PKM2 siRNA可有效提高Hippo信号通路活性,且抑制Hippo信号活性能明显逆转PKM2 siRNA抑制肝癌细胞增殖、侵袭和迁移能力。结论:PKM2可能通过抑制LATS1和YAP磷酸化,进而抑制Hippo信号通路,促进肝癌细胞增殖、侵袭和迁移能力。

    Abstract:

    Objective:To investigate effects and mechanisms of PKM2 on hepatocellular carcinoma(HCC)cell. Methods:PKM2 expression was detected in liver cancer tissues and liver cancer cell lines(HepG2,Hep3B,HuH7 and smmc-7721)by quantitative PCR(qPCR),Western blot(WB)and immunohistochemistry(IHC). PKM2 expression was inhibited by small interfering RNA(siRNA)in HCC cell lines. Effects of siRNA on the proliferation,invasion and migration was analyzed in HCC cell lines. In addition,we studied the effect of PKM2 siRNA on Hippo signaling pathway. Results:qPCR,WB and IHC showed PKM2 expression was significantly higher in HCC tissues than paracancer tissue,and in HCC cell lines than normal liver cell line(L02). PKM2 siRNA effectively inhibited the proliferation,invasion and migration of HCC cells. Further study confirmed that Hippo signaling activity was inhibited in HCC cell lines compared with L02,and was enhanced in PKM2 siRNA-treated HCC cell lines. Inhibition of Hippo signaling activity significantly reversed inhibition of proliferation,invasion and migration in PKM2 siRNA-mediated HCC cell lines. Conclusion:PKM2 may inhibit phosphorylation of LAST1 and YAP,decrease Hippo signaling pathway,and promote HCC cell proliferation,invasion and migration.

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欧 蓉,郁 飞,马 俊,穆四清,黄德松,倪绪浩,饶建华,管步高. PKM2抑制Hippo信号通路促进肝癌细胞增殖和侵袭迁移能力[J].南京医科大学学报(自然科学版),2019,(8):1183-1187

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  • 收稿日期:2019-04-30
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  • 在线发布日期: 2019-08-29
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