title: Aberrant expression of microRNA 155 may accelerate cell proliferation by targeting sex-determining region Y box 6 in hepatocellular carcinoma.
abstract: BACKGROUND
  Recent research has suggested that the oncomir microRNA 155 (miR-155) is up-regulated in hepatocellular carcinoma (HCC). In this study, the authors investigated the tumorigenic mechanism of this oncomir in the development of HCC.
  
  
  METHODS
  Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was conducted to analyze the expressions of miR-155 and its potential target genes in paired tumor tissues and adjacent tumor-free tissues and in disease-free liver tissue samples. The in silico predicted target genes of miR-155 were assessed by dual-luciferase reporting assay, real-time RT-PCR, and Western blot analyses. U6 promoters that drive miR-155 precursor overexpression and miR-155 tough decoy knock-down constructs were used to study its affects on cell proliferation in vitro and on tumor formation in nude mice.
  
  
  RESULTS
  Quantitative RT-PCR demonstrated a gradual ascension of miR-155 expression in cirrhotic liver tissues and in HCC tumor tissues compared with low expression levels in normal liver tissues. Ectopic expression of miR-155 in HepG2 cells enhanced its tumorigenesis, whereas depletion of the endogenous miR-155 reversed these tumorigenic properties. Ectopic expression of sex-determining region Y box 6 (SOX6) was able to reverse the growth-promoting property of miR-155. Concordantly, the results demonstrated for the first time that SOX6 is a direct target of miR-155. Further analysis revealed that SOX6 reduced cell growth by up-regulating p21waf1/cip1 expression in a p53-dependent manner. In addition, a decline in p21waf1/cip1 expression caused by miR-155 could be reversed by SOX6 expression.
  
  
  CONCLUSIONS
  The current data indicated that SOX6 is a novel target of miR-155 and that miR-155 enhances liver cell tumorigenesis at least in part through the novel miR-155/SOX6/p21waf1/cip1 axis. These findings suggest that miR-155 may be a potential target for HCC treatment.
authors: Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing, China.
authors: Qing
authors: Q
authors: Xie
authors: Xiangmei
authors: X
authors: Chen
authors: Fengmin
authors: F
authors: Lu
authors: Ting
authors: T
authors: Zhang
authors: Meili
authors: M
authors: Hao
authors: Yongfeng
authors: Y
authors: Wang
authors: Jingmin
authors: J
authors: Zhao
authors: Malcolm A
authors: MA
authors: McCrae
authors: Hui
authors: H
authors: Zhuang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000502:physiology; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009368:Neoplasm Transplantation; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D055755:SOXD Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C486270:SOX6 protein, human; D055755:SOXD Transcription Factors; D016283:Proto-Oncogene Proteins p21(ras)