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Int. J. Mol. Sci. 2015, 16(8), 19419-19432; doi:10.3390/ijms160819419

Lentiviral-Mediated Short Hairpin RNA Knockdown of MTDHInhibits Cell Growth and Induces Apoptosis by Regulatingthe PTEN/AKT Pathway in Hepatocellular Carcinoma

1
Department of Hepatibiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
2
Department of Cancer Research Center, Hubei Medical University, Shiyan 442000, China
3
State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, Shiyan 442000, China
*
Author to whom correspondence should be addressed.
Academic Editor: Alan C. Leonard
Received: 7 July 2015 / Accepted: 10 August 2015 / Published: 17 August 2015
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
View Full-Text   |   Download PDF [2446 KB, uploaded 17 August 2015]   |  

Abstract

The activation of oncogenes and the loss of tumor suppressor genes are believed toplay critical roles in the pathogenesis of human hepatocellular carcinoma (HCC). Metaherin (MTDH), also called astrocyte elevated gene-1 (AEG-1), is frequently amplified in a variety of cancers, but the roles of MTDH with regard to growth and apoptosis in HCC have not yet been studied. In the present study, we first analyzed the expression of MTDH in HCC samples. We found that MTDH protein levels are higher in most HCC cancerous tissues compared with their matched adjacent non-tumor tissues. Additionally, the MTDH mRNA was also higher in HCC tissues compared to their matched adjacent non-tumor tissues. Knockdown of the endogenous MTDH using small interfering RNA further showed that deficiency of MTDH suppressed cell growth and caused apoptosis in HCC cells. Knockdown MTDH promoted PTEN and p53 expression in HCC cells and inhibited AKT phosphorylation. Knockdown MTDH also inhibited tumor growth in vivo. All these results indicated that MTDH protein levels in most HCC tissues are higher than non-tumor tissues, and knockdown of MTDH inhibited growth and induced apoptosis in HCC cells through the activation of PTEN. Therefore, MTDH might be an effective targeted therapy gene for HCC. View Full-Text
Keywords: hepatocellular carcinoma; growth; apoptosis; metadherin hepatocellular carcinoma; growth; apoptosis; metadherin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Li, W.-F.; Ou, Q.; Dai, H.; Liu, C.-A. Lentiviral-Mediated Short Hairpin RNA Knockdown of MTDHInhibits Cell Growth and Induces Apoptosis by Regulatingthe PTEN/AKT Pathway in Hepatocellular Carcinoma. Int. J. Mol. Sci. 2015, 16, 19419-19432.

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