title: DAX-1 inhibits hepatocellular carcinoma proliferation by inhibiting β-catenin transcriptional activity.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) represents the most common type of liver cancer. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1), an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains, has been known for its fundamental roles in the development, especially in the sex determination and steroidogenesis. Previous studies also showed that DAX-1 played a critical role in endocrine and sex steroid-dependent neoplasms such as adrenocortical, pituitary, endometrial, and ovarian tumors. However, its biological roles in the development of HCC remain largely unexplored.
  
  
  METHODS
  Real-time PCR and Western blot were used to detect the expression of DAX-1 in HCC tissues and cell lines. Immunoprecipitation (IP) assay was used to show the interaction between DAX-1 and β-Catenin. Small interfering RNA (siRNA) was used to silence the expression of DAX-1. BrdU incorporation and Cell-cycle assays were used to detect the role of DAX-1 in HCC cells proliferation. Migration and invasion assays were carried out to test the metastasis ability of DAX-1 in HCC cells.
  
  
  RESULTS
  In the present study, we found that mRNA and protein levels of DAX-1 were down-regulated in HCC tissues and cell lines. Furthermore, overexpression of DAX-1 could inhibit while its knockdown using small interfering RNA promoted cell proliferation in several HCC cell lines. At the molecular level, we demonstrated that DAX-1 could interact with β-Catenin and attenuate its transcriptional activity.
  
  
  CONCLUSIONS
  Therefore, our results suggest a previously unknown DAX-1/β-Catenin molecular network controlling HCC development.
authors.affiliation: The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Jiang
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
authors.forename: Guo-Fu
authors.initials: GF
authors.lastname: Lin
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Ma
authors.forename: Jun-Zhe
authors.initials: JZ
authors.lastname: Jin
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D057137:DAX-1 Orphan Nuclear Receptor / Q000502:physiology*; D015536:Down-Regulation; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014158:Transcription, Genetic; D051176:beta Catenin / Q000235:genetics*
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; C539965:NR0B1 protein, human; D051176:beta Catenin