title: HCBP6 Modulates Triglyceride Homeostasis in Hepatocytes Via the SREBP1c/FASN Pathway.
abstract: Hypertriglyceridemia leads to liver steatosis, cardiovascular disease, and type 2 diabetes. Although HCBP6 (hepatitis C virus core-binding protein 6) was previously shown to be an HCV (hepatitis C virus) core-binding protein, its biological function remains unclear. Here, we demonstrate that HCBP6 negatively regulates intracellular triglyceride (TG) levels in hepatocytes. We found that bidirectional manipulation of hepatocyte HCBP6 expression by knockdown or overexpression results in increased or decreased TG accumulation, respectively. In addition, HCBP6 mRNA and protein levels exhibited significant time- and dose-dependent increases in a cellular model of lipid-overload hepatic steatosis. Furthermore, TG levels are regulated by HCBP6-sterol regulatory element binding protein 1c (SREBP1c)-mediated fatty acid synthase (FASN) expression. We also demonstrate that HCBP6 mRNA and protein expression is inhibited by microRNA-122 (miR-122), and miR-122 overexpression elicited more robust translational repression of luciferase activity driven by the full 3'-UTR of HCBP6. Taken together, our results provide new evidence that miR-122-regulated HCBP6 functions as a sensor protein to maintain intrahepatocyte TG levels.
authors: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors: Li-Li
authors: LL
authors: Gao
authors: The First Hospital of Lanzhou University, Gansu Province, Gansu, 730000, China.
authors: Min
authors: M
authors: Li
authors: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors: Qi
authors: Q
authors: Wang
authors: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors: Shun-Ai
authors: SA
authors: Liu
authors: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors: Jin-Qian
authors: JQ
authors: Zhang
authors: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors: Jun
authors: J
authors: Cheng
mesh_terms: D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism*; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000378:metabolism / Q000472:pathogenicity; D022781:Hepatocytes / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I
keywords: FATTY ACID; GENE EXPRESSION; LIPASE/HEPATIC; MicroRNA-122; NUCLEAR RECEPTORS/SREBP; TRIGLYCERIDES