title: Underexpressed microRNA-199b-5p targets hypoxia-inducible factor-1α in hepatocellular carcinoma and predicts prognosis of hepatocellular carcinoma patients.
abstract: OBJECTIVE
  MicroRNAs are short noncoding RNA molecules that are responsible for the posttranscriptional regulation of target genes. The aim of this study was to determine whether microRNA-199b-5p (miR-199b) plays a role in the progression and prognosis of hepatocellular carcinoma (HCC), and to elucidate whether hypoxia-inducible factor-1α (Hif1α) is regulated by miR-199b.
  
  
  METHODS
  In this study, 35 matched HCCs and cirrhosis tissues were assayed for miR-199b and Hif1α expression. To evaluate the role of miR-199b, we assessed cell proliferation rate and clonogenic survival of miR-199b- or negative control-transfected cells by MTT and clone formation assay, respectively. In addition, the regulation of Hif1α by miR-199b was evaluated by Western blotting and luciferase assay. MiR-199b was downregulated in 77% of HCCs, whereas Hif1α protein was upregulated in 69% of cases. A significant inverse correlation between miR-199b and Hif1α was observed in HCCs.
  
  
  RESULTS
  Patients with lower levels of miR-199b expression had poorer overall survival and progression-free survival rates, whereas patients with higher levels of miR-199b expression had better survival. Moreover, miR-199b could restrain cell growth and obviously enhance the radiosensitizing effect of HepG2 cells. MiR-199b and pGL3-Hif1α vector-transfected cells showed suppressed Hif1α protein expression and significant reduced luciferase activity.
  
  
  CONCLUSIONS
  Underexpressed miR-199b, which may be via the upregulation of Hif1α in HCCs, is inversely correlated with survival and directly correlated with the malignant status of HCC patients.
authors.affiliation: Department of Oncology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China.
authors.forename: Chuanxi
authors.initials: C
authors.lastname: Wang
authors.forename: Bao
authors.initials: B
authors.lastname: Song
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Aimin
authors.initials: A
authors.lastname: Sun
authors.forename: Dehua
authors.initials: D
authors.lastname: Wu
authors.forename: Huiming
authors.initials: H
authors.lastname: Yu
authors.forename: Jianping
authors.initials: J
authors.lastname: Lian
authors.forename: Longhua
authors.initials: L
authors.lastname: Chen
authors.forename: Junqing
authors.initials: J
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D016009:Chi-Square Distribution; D002681:China; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011836:Radiation Tolerance; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs; C531408:mirn199 microRNA, human