Knockdown of Myosin VI Inhibits Proliferation of Hepatocellular Carcinoma Cells In Vitro.

Abstract

Hepatocellular carcinoma is the primary malignancy of the liver and is the third leading cause of cancer-related death worldwide. Despite its severity, the treatment methods for hepatocellular carcinoma are limited due to poor prognosis. This study identified the short hairpin RNA-mediated silencing of myosin VI as a potential approach for the treatment of hepatocellular carcinoma. Firstly, the expression of myosin VI was analyzed in 57 hepatocellular carcinoma samples and 10 non-neoplastic samples by immunohistochemistry. The results demonstrated that myosin VI expression was much stronger in hepatocellular carcinoma tissues than in adjacent normal tissues. Myosin VI short hairpin RNA was then transduced into HepG2 and SMMC-7721 hepatocellular carcinoma cell lines, respectively, using a lentivirus delivery system. Knockdown of myosin VI led to a significant reduction in cell proliferation and colony-forming capacity, as well as a blockade of cell cycle progression. Moreover, an obvious decrease in PRAS40 phosphorylation and a concomitant increase in p38 phosphorylation were observed in myosin VI knockdown cells, which suggest that myosin VI silencing inhibits hepatocellular carcinoma cell growth in vitro probably via inactivation of PRAS40 and activation of p38 mitogen-activated protein kinase-dependent signaling pathway. This study highlights the potential of myosin VI to be developed as a target for hepatocellular carcinoma therapy.

• Authors: Xiaoming Ma, Jiqi Yan, Wei Chen, Peng Du, Jiaming Xie, Hongpei Yu, Haorong Wu
• Journal: Chemical biology & drug design (Chem Biol Drug Des) Vol. 86 Issue 4 Pg. 723-30 (Oct 2015) ISSN: 1747-0285 [Electronic] England
• PMID: 25703929 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons A/S.

Chemical References

• AKT1S1 protein, human
• Adaptor Proteins, Signal Transducing
• myosin VI
• p38 Mitogen-Activated Protein Kinases
• Myosin Heavy Chains

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Carcinoma, Hepatocellular (genetics, pathology)
• Cell Cycle (genetics)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Cell Survival (genetics)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Lentivirus (genetics)
• Liver Neoplasms (genetics, pathology)
• Molecular Targeted Therapy (methods)
• Myosin Heavy Chains (genetics, metabolism)
• Phosphorylation
• Signal Transduction (genetics)
• p38 Mitogen-Activated Protein Kinases (metabolism)