title: Prognostic marker microRNA-125b inhibits tumorigenic properties of hepatocellular carcinoma cells via suppressing tumorigenic molecule eIF5A2.
abstract: BACKGROUND
  MicroRNAs (miRNAs) belong to a group of small non-coding RNA with differential expression in tumors, including hepatocellular carcinoma (HCC).
  
  
  OBJECTIVE
  This study investigates the involvement of miR-125b in HCC.
  
  
  METHODS
  Clinical analysis of miR-125b was performed using data derived from miRNA profiling and qPCR. Phenotypic changes of liver cell lines were examined after ectopic miR-125b expression. Lastly, bioinformatics analysis coupled with luciferase reporter assay was used to reveal the cellular target of miR-125b.
  
  
  RESULTS
  A down-regulation of miR-125b was found in HCC tumors and cultured cells. Patients having tumors with ≥twofold reduction in miR-125b compared to adjacent non-tumor tissues contributed to 23 out of 49 HCC cases (46.9 %), while this down-regulation was usually found in patients with tumor venous infiltration and recurrence. miR-125b expression was also negatively correlated with increased serum AFP level and poor overall survival of patients. Ectopic expression of miR-125b led to alleviated tumor phenotypes of HCC cells. Among the 110 bioinformatically predicated candidates, 31 of them negatively correlated with miR-125b in HCC tumors for which one of them named eukaryotic translation initiation factor 5A2 (eIF5A2), known also as a liver oncofetal molecule, was validated to be a direct target of miR-125b in HCC.
  
  
  CONCLUSIONS
  This study has evidenced for the negative correlation of tumor miR-125b expression with poor prognosis of HCC patients. Expression of miR-125b can reverse the tumorigenic properties of cultured HCC cells via suppressing the tumorigenic molecule eIF5A2, thus postulating restoration of miR-125b level as a way to counteract liver tumorigenesis.
authors.affiliation: Department of Surgery, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong.
authors.forename: Felice H
authors.initials: FH
authors.lastname: Tsang
authors.forename: Victor
authors.initials: V
authors.lastname: Au
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Lu
authors.forename: Felix H
authors.initials: FH
authors.lastname: Shek
authors.forename: Angela M
authors.initials: AM
authors.lastname: Liu
authors.forename: John M
authors.initials: JM
authors.lastname: Luk
authors.forename: Sheung-Tat
authors.initials: ST
authors.lastname: Fan
authors.forename: Ronnie T P
authors.initials: RT
authors.lastname: Poon
authors.forename: Nikki P
authors.initials: NP
authors.lastname: Lee
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D010448:Peptide Initiation Factors; C425967:eIF-5A2