Knockdown MTMR14 promotes cell apoptosis and inhibits migration in liver cancer cells
Zhaodong Li1, Li Rong2, Haifeng Lian3
1Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, 74#Linjiang Road, Yuzhong District, Chongqing City 400001, PR China.
Abstract:
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.
Insights
Myotubularin-related protein 14 (MTMR14) is overexpressed in liver cancer, promoting cell migration and inhibiting apoptosis. Targeting MTMR14 may offer new diagnostic and therapeutic strategies for liver cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Myotubularin-related protein 14 (MTMR14), a member of the myotubularin family, is implicated in cardiomyopathy and autophagy.
- The role of MTMR14 in human cancer, particularly liver cancer, remains largely unexplored.
Purpose of the Study:
- To investigate the expression profile of MTMR14 in liver cancer.
- To elucidate the functional impact of MTMR14 on liver cancer cell behavior and underlying molecular mechanisms.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry for expression analysis.
- Loss-of-function studies (MTMR14 knockdown) in vitro and in vivo.
- Western blot analysis to assess protein expression changes and pathway activation.
Main Results:
- MTMR14 is significantly overexpressed in liver cancer tissues and correlates with advanced clinical stage.
- MTMR14 knockdown suppresses liver cancer cell migration and promotes apoptosis via the mitochondrial pathway.
- Mechanistically, MTMR14 knockdown affects N-cadherin and E-cadherin expression and modulates caspase activation.
Conclusions:
- MTMR14 exhibits an oncogenic role in human liver cancer.
- MTMR14 influences cell migration and apoptosis through specific molecular pathways.
- MTMR14 represents a potential diagnostic and therapeutic target for liver cancer.
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