title: MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying HCC progression are still not completely clear. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of a metastasis-associated miRNA named miR-188-5p in HCC.
  
  
  METHODS
  miRNA array analysis was performed to search for metastasis-associated miRNAs in HCC. miR-188-5p expressions in tumor tissues and adjacent non-tumorous liver tissues of HCC patients and cell lines were evaluated by real-time PCR. The protein expression levels were analyzed by Western blot and immunohistochemistry. Luciferase reporter assays was used to validate the target of miR-188-5p. The effect of miR-188-5p on HCC progression was studied in vitro and in vivo.
  
  
  RESULTS
  miR-188-5p was significantly decreased in HCC and its expression levels were highly correlated with multiple nodules, microvascular invasion, overall and disease-free survival of HCC. Ectopic expression of miR-188-5p suppressed HCC cell proliferation and metastasis in vitro and in vivo. Fibroblast growth factor 5 (FGF5) was identified as a major target of miR-188-5p. Enforced expression of miR-188-5p inhibited the expression of FGF5 significantly and the restoration of FGF5 expression reversed the inhibitory effects of miR-188-5p on HCC cell proliferation and metastasis.
  
  
  CONCLUSIONS
  These findings collectively demonstrate a tumor suppressor role of miR-188-5p in HCC progression via targeting FGF5, suggesting that miR-188-5p could serve as a potential prognostic biomarker and therapeutic target for HCC.
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Fang
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Rui-min
authors.initials: RM
authors.lastname: Chang
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Lei
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: lianyueyang@hotmail.com.
authors.forename: Lian-Yue
authors.initials: LY
authors.lastname: Yang
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D051521:Fibroblast Growth Factor 5 / Q000096:biosynthesis / Q000235:genetics*; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies
chemical_list: C496449:FGF5 protein, human; C584093:MIRN188 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D051521:Fibroblast Growth Factor 5
keywords: Cohort; Fibroblast growth factor 5; MicroRNA; Prognosis; Solitary large hepatocellular carcinoma