异质核核糖核蛋白L促进肝细胞癌细胞增殖的机制研究  

Study on the mechanism of heterogeneous nuclear ribonucleoprotein L promoting the proliferation of hepatocellular carcinoma cells

作　　者：陈加新[1] 胡嵩[1] 刘赋斌 马振威 杨康 邹声泉 熊飞[4] 王兵[4] Chen Jiaxin;Hu Song;Liu Fubin;Ma Zhenwei;Yang Kang;Zou Shengquan;Xiong Fei;Wang Bing(Department of General Surgery,Ezhou Central Hospital,Ezhou 436099,China;Department of Hepatobiliary and Pancreatic Surgery,Tianyou Hospital,Wuhan University of Science and Technology,Wuhan 430000,China;Department of Hepatobiliary Surgery,Zhangjiajie People's Hospital,Zhangjiajie 427000,China;Department of Biliary and Pancreatic Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]鄂州市中心医院普外一科,鄂州436099 [2]武汉科技大学附属天佑医院肝胆胰外科,武汉430000 [3]张家界市人民医院肝胆外科,张家界427000 [4]华中科技大学同济医学院附属同济医院胆胰外科,武汉430030

出　　处：《中华肝胆外科杂志》2023年第9期694-699,共6页Chinese Journal of Hepatobiliary Surgery

基　　金：国家自然科学基金(81502108)。

摘　　要：目的探究异质核核糖核蛋白L(HNRNPL)蛋白对原发性肝细胞癌(HCC)细胞增殖能力的影响及潜在机制。方法利用公共数据库和实时定量PCR分析HNRNPL在HCC和癌旁组织间的表达差异;利用蛋白免疫印迹、细胞计数、平板克隆和裸鼠成瘤实验检测敲减HNRNPL对HCC细胞MHCC97H、HepG2增殖和丝裂原活化蛋白激酶(MAPK)通路的影响。结果HCC组织中HNRNPL的mRNA水平(2.76±0.37)高于正常组织(1.00±0.14),差异具有统计学意义(t=3.93,P=0.002)。平板克隆实验显示两组敲减HNRNPL表达的MHCC97H细胞集落数分别为(33.3±7.7)、(43.3±2.2),低于对照组(84.3±6.2);两组HepG2敲减细胞的集落数分别为(59.0±15.5)、(41.7±4.8),低于对照组(200.3±6.2),差异均有统计学意义(均P<0.01)。敲减HNRNPL表达降低了HCC细胞增殖能力和MAPK通路的活化水平,而过表达原癌基因c-RAF可部分缓解敲减HNRNPL的细胞增殖抑制作用,挽救HCC细胞的成瘤能力。结论HNRNPL通过激活MAPK信号通路促进HCC细胞增殖。Objective To investigate the effect of HNRNPL protein on the proliferative ability of primary hepatocellular carcinoma cells and its potential mechanism.Methods Online public database and real-time quantitative PCR were used to analyze the difference of HNRNPL expression between cancer and adjacent tissues.The effects of HNRNPL on HCC cell MHCC97H and HepG2 proliferation and MAPK pathway were investigated by Western blot,cell counting assay,colony formation assay and nude mouse transplantation tumor experiments.Results The level of HNRNPL mRNA was validated to be higher in HCC tissue(2.76±0.37)than in normal tissue(1.00±0.14)with statistical difference(t=3.93,P=0.002).Colony formation assay showed that the colony numbers of two MHCC97H knockdown groups(33.3±7.7)and(43.3±2.2)were lower than their control group(84.3±6.2),and two HepG2 knockdown groups(59.0±15.5)and(41.7±4.8)were lower than their control group(200.3±6.2)with statistical difference(both P<0.01).HNRNPL knockdown decreased the proliferation ability and activation level of MAPK pathway in HCC cells.Overexpression of oncogene c-RAF partially alleviated the anti-proliferation effect of HNRNPL knockdown and rescued the tumorigenic capacity.Conclusion HNRNPL can promote hepatocellular carcinoma cell proliferation by activating MAPK signaling pathway.

关 键 词：癌 肝细胞 异质核核糖核蛋白L 增殖 

分 类 号：R735.7[医药卫生—肿瘤]