Knockdown MTMR14 promotes cell apoptosis and inhibits migration in liver cancer cells
Knockdown MTMR14 promotes cell apoptosis and inhibits migration in liver cancer cells
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DOI：
10.1016/j.gene.2018.11.099
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发表时间：
2019-04-05
期刊：
影响因子：
3.5
通讯作者：
Li, Xiang
中科院分区：
文献类型：
--
作者：
Li, Zhaodong;Rong, Li;Li, Xiang
肌小管蛋白相关蛋白14(MTMR14)是肌小管蛋白(MTM)相关蛋白家族的成员，在心肌病和自噬中起关键作用。然而，它对人类癌症的潜在影响尚不清楚。在本研究中，我们首次研究了MTMR14在肝癌中的表达及其对功能的影响。实时定量聚合酶链式反应(qRT-PCR)和免疫组织化学分析表明，MTMR14在肝癌组织中明显过表达，并与临床分期呈正相关。一项功能丧失的研究表明，MTMR14基因敲除促进了细胞凋亡，抑制了细胞迁移。MTMR14基因敲除也能抑制裸鼠肝癌腹膜移植瘤的体内转移。蛋白质印迹分子机制研究表明，MTMR14基因敲除后，N-钙粘蛋白和E-钙粘蛋白的表达下调，caspase12、caspase9和caspase3的切割和激活作用增强，但不包括caspase8。这些结果提示MTMR14通过N-钙粘蛋白和E-钙粘蛋白影响细胞迁移。另外，MTMR14通过线粒体途径影响细胞的凋亡，而不是死亡受体途径。在此，我们的结果表明MTMR14在人类肝癌中可能具有致癌作用，从而显示其作为肝癌诊断和/或治疗的靶点的潜力。
Myotubularin-related protein 14 (MTMR14) is a member of the myotubularin (MTM)-related protein family and plays a key role in cardiomyopathy and autophagy. However, its potential implication in human cancer is unclear. In this study, we have investigated the expression profile of MTMR14 and its functional impact in liver cancer for the first time. Expression analysis by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry demonstrated that MTMR14 expression is obviously overexpressed in liver cancer, and positively correlated with clinical stage. A loss-of-function study showed that knockdown of MTMR14 promotes cell apoptosis and inhibits cell migration. MTMR14 knockdown also inhibits tumor migration in vivo in liver cancer peritoneal implantation nude mouse model. A molecular mechanistic study by western blot showed that Knockdown MTMR14 causes downregulation of N-cadherin and E-cadherin, and promotes the cleavage and activation of caspase12, caspase9 and caspase3, but excluding caspase8. These results suggest that MTMR14 affects cell migration through N-cadherin and E-cadherin. Additionally, MTMR14 affects cell apoptosis through mitochondrial pathway but not the death receptor pathway. Herein, our results indicate MTMR14 could have an oncogenic role in human liver cancer and thus demonstrates its potential as a target for the diagnosis and/or treatment of liver cancer.