Oncotarget

Research Papers:

HBV preS2 promotes the expression of TAZ via miRNA-338-3p to enhance the tumorigenesis of hepatocellular carcinoma

Peng Liu, Hualin Zhang, Xiaohong Liang, Hongxin Ma, Fang Luan, Bo Wang, Fuxiang Bai, Lifen Gao and Chunhong Ma _

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Oncotarget. 2015; 6:29048-29059. https://doi.org/10.18632/oncotarget.4804

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Abstract

Peng Liu1, Hualin Zhang1, Xiaohong Liang1, Hongxin Ma1, Fang Luan2, Bo Wang1, Fuxiang Bai1, Lifen Gao1, Chunhong Ma1

1Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, 250012, P.R. China

2Department of Clinical Laboratory, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, 250021, P.R. China

Correspondence to:

Chunhong Ma, e-mail: [email protected]

Keywords: preS2, miRNA-338-3p, HCC, Hippo pathway, TAZ

Received: January 14, 2015     Accepted: July 24, 2015     Published: August 05, 2015

ABSTRACT

Transactivators encoded by HBV, including HBx and preS2, play critical role in hepatocellular carcinoma (HCC). YAP, a downstream effector of the Hippo pathway, is involved in hepatocarcinogenesis mediated by HBx. Here, we investigated whether preS2, another transactivator encoded by HBV, regulates the Hippo pathway to promote HCC. We found that preS2 overexpression upregulated TAZ, a downstream effector of the Hippo pathway, at protein level but not at mRNA level. preS2 suppressed miRNA-338-3p expression in HCC cell lines. miRNA-338-3p mimics downregulated TAZ, while miRNA-338-3p inhibitor restored the expression of TAZ, suggesting that TAZ is a direct target of miRNA-338-3p. TAZ overexpression stimulated growth of HCC cell lines. Knockdown of TAZ dampened preS2-promoted HCC proliferation and migration. Thus, preS2 upregulates TAZ expression by repressing miRNA-338-3p. TAZ is necessary for preS2-promoted HCC proliferation and migration


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