title: The X protein of hepatitis B virus activates hepatoma cell proliferation through repressing melanoma inhibitory activity 2 gene.
abstract: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths globally. Chronic hepatitis B virus (HBV) infection accounts for over 75% of all HCC cases; however, the molecular pathogenesis of HCC is not well understood. In this study, we found that the expression of the newly identified gene melanoma inhibitory activity 2 (MIA2) was reduced by HBV infection in vitro and in vivo, and that HBV X protein (HBx) plays a major role in this regulation. Recent studies have revealed that MIA2 is a potential tumor suppressor, and that, in most HCCs, MIA2 expression is down-regulated or lost. We found that the knock-down of MIA2 in HepG2 cells activated cell growth and proliferation, suggesting that MIA2 inhibits HCC cell growth and proliferation. In addition, the over-expression of HBx alone induced cell proliferation, whereas MIA2 over-expression impaired the HBx-mediated induction of proliferation. Taken together, our results suggest that HBx activates hepatoma cell growth and proliferation through repression of the potential tumor suppressor MIA2.
authors: State Key Laboratory of Virology, College of Life Sciences, and Chinese-French Liver Disease Research Institute at Zhongnan Hospital, Wuhan University, Wuhan 430072, PR China.
authors: Yilin
authors: Y
authors: Xu
authors: Yang
authors: Y
authors: Yang
authors: Yanyan
authors: Y
authors: Cai
authors: Fang
authors: F
authors: Liu
authors: Yingle
authors: Y
authors: Liu
authors: Ying
authors: Y
authors: Zhu
authors: Jianguo
authors: J
authors: Wu
mesh_terms: D000951:Antigens, Neoplasm; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000821:virology*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000821:virology*; D009363:Neoplasm Proteins; D015534:Trans-Activators / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D000951:Antigens, Neoplasm; C109278:MIA2 protein, human; D009363:Neoplasm Proteins; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein