title: The expression level of miR-18b in hepatocellular carcinoma is associated with the grade of malignancy and prognosis.
abstract: BACKGROUND
  Many studies support the hypothesis that specific microRNA (miRNA) expression in various human cancers including hepatocarcinogenesis is closely associated with diagnosis and prognosis. In hepatocellular carcinoma (HCC), malignancy level is related to the degree of histological differentiation.
  
  
  METHODS
  In order to establish a novel biomarker that can determine the degree of malignancy and forecast patient prognosis, we performed a microarray analysis to investigate the miRNA expression profiles in 110 HCC which were comprised of 60 moderately, 30 poorly, and 20 well differentiated HCC.
  
  
  RESULTS
  We found that the expression of 12 miRNAs varied significantly according to the degree of histological differentiation. Particularly, miR-18b expression in poorly differentiated HCC was significantly higher than in well differentiated HCC. Based on miRanda and Targetscan target search algorithms and Argonaute 2 immunoprecipitation study, we noted that miR-18b can control the expression of trinucleotide repeat containing 6B (TNRC6B) as a target gene. Additionally, in two hepatoma cell lines, we found that over-expression of miR-18b or down-regulation of TNRC6B accelerated cell proliferation and loss of cell adhesion ability. Finally, we observed that after surgical resection, HCC patients with high miR-18b expression had a significantly shorter relapse-free period than those with low expression.
  
  
  CONCLUSIONS
  miR-18b expression is an important marker of cell proliferation and cell adhesion, and is predictive of clinical outcome. From a clinical point of view, our study emphasizes miR-18b as a diagnostic and prognostic marker for HCC progression.
authors.affiliation: Department of Hepatology, Graduate School of Medicine Osaka City University, Osaka 545-8585, Japan. m2079633@med.osaka-cu.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakami
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamori
authors.forename: Saori
authors.initials: S
authors.lastname: Itami
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyoda
authors.forename: Masami
authors.initials: M
authors.lastname: Tanaka
authors.forename: Weihong
authors.initials: W
authors.lastname: Wu
authors.forename: Nariso
authors.initials: N
authors.lastname: Brojigin
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kaneoka
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Maeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumada
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.forename: Shoji
authors.initials: S
authors.lastname: Kubo
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kuroda
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D011379:Prognosis; D012334:RNA, Neoplasm / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C581632:MIRN18 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm