Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, 74#Linjiang Road, Yuzhong District, Chongqing City 400001, PR China.
Department of Gastroenterology, Chongqing Infectious Disease Medical Center, Chongqing City 400030, PR China.
Gene. 2019 Apr 5;691:106-113. doi: 10.1016/j.gene.2018.11.099. Epub 2018 Dec 23.
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.
肌管素相关蛋白 14（MTMR14）是肌管素（MTM）相关蛋白家族的成员，在心肌病和自噬中发挥关键作用。然而，其在人类癌症中的潜在作用尚不清楚。在这项研究中，我们首次研究了 MTMR14 的表达谱及其在肝癌中的功能影响。通过定量实时聚合酶链反应（qRT-PCR）和免疫组织化学分析表明，MTMR14 在肝癌中明显过表达，并与临床分期呈正相关。功能丧失研究表明，MTMR14 的敲低促进细胞凋亡并抑制细胞迁移。MTMR14 敲低也抑制肝癌腹膜种植裸鼠模型中的肿瘤迁移。Western blot 的分子机制研究表明，敲低 MTMR14 导致 N-钙黏蛋白和 E-钙黏蛋白下调，并促进 caspase12、caspase9 和 caspase3 的切割和激活，但不包括 caspase8。这些结果表明 MTMR14 通过 N-钙黏蛋白和 E-钙黏蛋白影响细胞迁移。此外，MTMR14 通过线粒体途径而不是死亡受体途径影响细胞凋亡。因此，我们的结果表明 MTMR14 在人类肝癌中具有致癌作用，因此表明其作为肝癌诊断和/或治疗靶点的潜力。
