Oncogenic role of phospholipase C-gamma 1 in progression of hepatocellular carcinoma
Oncogenic role of phospholipase C-gamma 1 in progression of hepatocellular carcinoma
复制标题
磷脂酶 C–γ1 在肝细胞癌进展中的致癌作用
DOI：
10.1111/hepr.13309
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发表时间：
2019
影响因子：
4.2
通讯作者：
Yang Biwei
中科院分区：
文献类型：
--
作者：
Tang Wenqing;Zhou Yi;Sun Dalong;Dong Ling;Xia Jinglin;Yang Biwei
磷脂酶C-γ1(PLCG1)参与多种致癌行为，如细胞运动、细胞增殖、细胞迁移和侵袭等。然而，其在肝细胞癌中的作用尚不清楚。方法采用免疫印迹法检测PLCG1在肝癌细胞和人肿瘤组织中的表达。采用免疫组织化学方法检测150例肝细胞癌临床标本中的表达，并分析其临床意义。通过体内外实验观察PLCG1对肝癌发生的影响。结果PLCG1在肝癌细胞系和临床肝细胞癌组织中高表达。PLCG1在肿瘤组织中的高表达与肝细胞癌的不良临床特征显著相关。肿瘤组织中PLCG1表达阳性的患者总生存期和无复发生存期较短。磷脂酶C-γ1在体外能显著促进细胞增殖、锚定生长和细胞侵袭。体内实验表明，PLCG1在肝癌细胞中的抑制作用显著抑制裸鼠移植瘤的生长。结论PLCG1可作为癌基因在肝细胞癌的发生发展过程中发挥作用，可作为一种有价值的预后标志物和潜在的治疗靶点。
AimPhospholipase C‐γ1 (PLCG1) was previously found to be involved in a variety of oncogenic behaviors such as cell motility, cell proliferation, cell migration, and invasion. However, its function in hepatocellular carcinoma (HCC) was unknown. Here, we explored the expression pattern and function of PLCG1 in HCC progression.MethodsExpression of PLCG1 was examined by western blotting in hepatoma cells and human tumor tissues. Expression was also detected by immunohistochemistry in 150 HCC clinical samples, and its clinical significance was analyzed. The influence of PLCG1 on HCC carcinogenesis were determinedin vitroandin vivo. The underlying mechanisms were explored by detecting the expression of critical molecules of signaling pathways.ResultsThe results showed that PLCG1 was overexpressed in hepatoma cell lines and clinical HCC tissues. Increased PLCG1 expression in tumor tissues was remarkably correlated with poor clinical features of HCC. Patients with positive PLCG1 expression in tumor tissues had shorter overall survival and relapse‐free survival. Phospholipase C gamma 1 could substantially promote cell proliferation, anchor growth, and cell invasionin vitro. Thein vivostudy showed that inhibition of PLCG1 in hepatoma cells significantly repressed tumor growth in nude mice. Furthermore, we showed that PLCG1 might exert its function by activating the mitogen‐activated protein kinase and nuclear factor‐κB signaling pathways.ConclusionOur data indicated thatPLCG1could act as an oncogene in HCC carcinogenesis and could serve as a valuable prognostic marker and potential therapeutic target for HCC.