title: Hepatitis C virus core protein impairs metabolic disorder of liver cell via HOTAIR-Sirt1 signalling.
abstract: It has been suggested that Hepatitis C virus (HCV) core protein is associated with metabolic disorders of liver cell. However, the precise mechanism is still unclear. The aim of the present study was to explore the impact of HCV core protein on hepatocyte metabolism by HepG2 and the possible involvement of long non-coding (lnc) RNAs in this process. The effect of HCV core protein on lncRNAs expression was examined with quantitative RT-PCR (qRT-PCR). Manipulation of HVC core protein and lncRNA HOTAIR was to evaluate the role of interaction between them on cell metabolism-related gene expression and cellular metabolism. The potential downstream Sirt1 signal was examined by western blotting and qRT-PCR. Our data suggested that suppression of HOTAIR abrogates HCV core protein-induced reduction in Sirt1 and differential expression of glucose- and lipid-metabolism-related genes. Also it benefits for metabolic homoeostasis of hepatocyte indicated by restoration of cellular reactive oxygen species (ROS) level and NAD/NADH ratio. By manipulation of HOTAIR, we concluded that HOTAIR negatively regulates Sirt1 expression through affecting its promotor methylation. Moreover, overexpression of Sirt1 reverses pcDNA-HOTAIR-induced glucose- and lipid-metabolism-related gene expression. Our study suggests that HCV core protein causes dysfunction of glucose and lipid metabolism in liver cells through HOTAIR-Sirt1 signalling pathway.
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Li
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Gu
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Jin-Xing
authors.initials: JX
authors.lastname: Hu
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ping
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Jing-Ya
authors.initials: JY
authors.lastname: Yan
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Zu-Jing
authors.initials: ZJ
authors.lastname: Yu
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China School of Life Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China Key Laboratory of Clinical-Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China zhanhyi052@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D019175:DNA Methylation; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D050356:Lipid Metabolism; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014758:Viral Core Proteins / Q000378:metabolism*
chemical_list: C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding; D017382:Reactive Oxygen Species; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005947:Glucose
keywords: HCV core protein; HOTAIR; HepG2; metabolism