title: MicroRNA-449 suppresses proliferation of hepatoma cell lines through blockade lipid metabolic pathway related to SIRT1.
abstract: MicroRNA (miRNA or miR) inhibition of oncogenic related pathways has been shown to be a promising therapeutic approach for cancer. SIRT1 might be a promoter factor on tumorigenesis of hepatocellular carcinoma (HCC). However, the mechanism is unknown. We investigated whether miRNAs regulate the SIRT1 and its downstream SREBP-lipogenesis-cholesterogenesis metabolic pathway in hepatoma cells. Human hepatoma cells were transfected with miR-449 mimics and inhibitors, and the effects of miR-449 on cell proliferation was assessed. We identified the miRNAs, miR-449, that control lipogenesis and cholesterogenesis in hepatoma cells by inhibiting SIRT1 and SREBP-1c expression and downregulating their targeted genes, including fatty acid synthase (FASN) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). MiR-449 repressed DNA synthesis, mitotic entry and proliferation of hepatoma cells. Restoration of miR-449 led to suppression of SIRT1 expression and liver tumorigenesis. The newly identified miRNAs, miR-449 represents a novel targeting mechanism for HCC therapy.
authors.affiliation: Department of Hepatobiliary Surgery, Air Force General Hospital, Beijing 100142, P.R. China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Air Force General Hospital, Beijing 100142, P.R. China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Guoan
authors.initials: G
authors.lastname: Xiang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors.forename: Jinqian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000235:genetics; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C544530:MIRN449 microRNA, human; D035683:MicroRNAs; D051779:Sterol Regulatory Element Binding Proteins; C447939:SIRT1 protein, human; D056564:Sirtuin 1