title: MicroRNA-145 suppresses hepatocellular carcinoma by targeting IRS1 and its downstream Akt signaling.
abstract: Accumulating evidences have proved that dysregulation of microRNAs (miRNAs) is involved in cancer initiation and progression. In this study, we showed that miRNA-145 level was significantly decreased in hepatocellular cancer (HCC) tissues and cell lines, and its low expression was inversely associated with the abundance of insulin receptor substrate 1 (IRS1), a key mediator in oncogenic insulin-like growth factor (IGF) signaling. We verified IRS1 as a direct target of miR-145 using Western blotting and luciferase reporter assay. Further, the restoration of miR-145 in HCC cell lines suppressed cancer cell growth, owing to down-regulated IRS1 expression and its downstream Akt/FOXO1 signaling. Our results demonstrated that miR-145 could inhibit HCC through targeting IRS1 and its downstream signaling, implicating the loss of miR-145 regulation may be a potential molecular mechanism causing aberrant oncogenic signaling in HCC.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yelin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Binquan
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Ke
authors.affiliation: Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: zyfhdj@yahoo.com.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Forkhead box protein O1 (FOXO1); Hepatocellular carcinoma (HCC); Insulin receptor substrate 1 (IRS1); MicroRNA-145