title: Involvement of cholesterol in hepatitis B virus X protein-induced abnormal lipid metabolism of hepatoma cells via up-regulating miR-205-targeted ACSL4.
abstract: Hepatitis B virus X protein (HBx) plays crucial roles in the development of hepatocellular carcinoma (HCC). The abnormal lipid metabolism is involved in the hepatocarcinogenesis. We previously reported that HBx suppressed miR-205 in hepatoma cells. In this study, we supposed that HBx-decreased miR-205 might contribute to the abnormal lipid metabolism according to the bioinformatics analysis. Interestingly, we showed that the expression levels of acyl-CoA synthetase long-chain family member 4 (ACSL4) were negatively associated with those of miR-205 in clinical HCC tissues. Then, we validated that miR-205 was able to inhibit the expression of ACSL4 at the levels of mRNA and protein through targeting its 3'UTR. Strikingly, we found that HBx was able to increase the levels of cellular cholesterol, a metabolite of ACSL4, in hepatoma cells, which could be blocked by miR-205 (or Triacsin C, an inhibitor of ACSL4). However, anti-miR-205 could increase the levels of cholesterol in the cells. Moreover, we demonstrated that the levels of cholesterol were increased in the liver of HBx transgenic mice in a time course manner. Functionally, oil red O staining revealed that HBx promoted lipogenesis in HepG2 cells, which could be abolished by miR-205 (or Triacsin C). However, anti-miR-205 was able to accelerate lipogenesis in the cells. Interestingly, the treatment with Triacsin C could remarkably block the role of anti-miR-205 in the event. Thus, we conclude that miR-205 is able to target ACSL4 mRNA. The HBx-depressed miR-205 is responsible for the abnormal lipid metabolism through accumulating cholesterol in hepatoma cells.
authors.affiliation: Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Zelin
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Baodi
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Minying
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China. Electronic address: zhangxd@nankai.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002784:Cholesterol / Q000378:metabolism*; D003066:Coenzyme A Ligases / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000150:complications; D006515:Hepatitis B virus / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D020413:3' Untranslated Regions; D002784:Cholesterol; D003066:Coenzyme A Ligases; D035683:MicroRNAs; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; C534425:MIR205, human; C057628:hepatitis B virus X protein
keywords: ACSL4; Abnormal lipid metabolism; Choleterol; HBx; Hepatocellular carcinoma; miR-205