title: microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity.
abstract: BACKGROUND
  Recently, microRNAs in cancer development have attracted much attention, but their roles in tumorigenesis are still largely unknown. In this study, a functional role of miR-22 in hepatocellular carcinoma (HCC) development has been identified.
  
  
  METHODS
  Quantitative real-time PCR was used to determine the level of miR-22 transcript in HCC clinical samples, and its correlation with disease-free survival was determined using Kaplan-Meier method. Restoration of miR-22 expression was carried out in HCC cell lines to assess its influence on HCC cell proliferation and tumourigenicity.
  
  
  RESULTS
  In the 160 paired HCC tissue samples, miR-22 expression was downregulated in HCC, and low miR-22 expression in HCC was predictive of poor survival in HCC patients. Functional studies indicated that ectopic expression of miR-22 significantly inhibits HCC cell proliferation and tumourigenicity. Furthermore, histone deacetylase 4 (HDAC4), known to have critical roles in cancer development, was proved to be directly targeted and regulated by miR-22. Furthermore, HDAC4 was upregulated in miR-22-downregulated HCC tissues, suggesting that downregulation of miR-22 might participate in HCC carcinogenesis and progression through potentiation of HDAC4 expression. In addition, cell proliferation was also suppressed by knockdown of HDAC4 or treatment with HDAC inhibitor trichostatin A in HCC cell lines.
  
  
  CONCLUSIONS
  miR-22, downregulated in HCC, has an anti-proliferative effect on HCC cells both in vitro and in vivo. Furthermore, miR-22 may have considerable potential in identification of the prognosis and application of cancer therapy for HCC patients.
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: T
authors.initials: T
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Fu
authors.forename: M
authors.initials: M
authors.lastname: Wu
authors.forename: Z
authors.initials: Z
authors.lastname: Pan
authors.forename: W
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011379:Prognosis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C548375:MIRN22 microRNA, human; D035683:MicroRNAs