title: Downregulation of ARNT2 promotes tumor growth and predicts poor prognosis in human hepatocellular carcinoma.
abstract: OBJECTIVE
  Aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) is a transcriptional regulator and member of the basic helix-loop-helix/Per-ARNT-SIM (bHLH/PAS) superfamily. Recently, evidence of that ARNT is involved in carcinogenesis and cancer progression has emerged. The aim of current study was to investigate the role of ARNT2, a homolog of ARNT, in tumor growth, invasion, and prognosis of hepatocellular carcinoma (HCC).
  
  
  METHODS
  Tissue microarray and immunohistochemical staining were used to examine the expression of ARNT2 in 195 HCC tissues. Factors associated with ARNT2 levels were assessed by univariate and multivariate Cox regression analyses. Cell proliferation, migration, and invasion assays were performed by using ARNT2 silencing and overexpressing HCCLM6 cell line. Orthotopic xenograft HCC model was used to elucidate the effects of ARNT2 on HCC progression in vivo.
  
  
  RESULTS
  High intratumoral of ARNT2 level was well correlated with longer overall survival (OS) and lower tumor to recurrence (TTR) of HCC patients after resection. Multivariate analysis revealed that intratumoral ARNT2 overexpression was an independent prognostic factor for both OS and TTR. Knockdown of ARNT2 in HCCLM6 cells was significantly enhanced while overexpression of ARNT2 significantly inhibited the ability of cell proliferation, invasion, and migration. In animal studies, downregulation of ARNT2 in HCCLM6 cells promoted, whereas upregulation of ARNT2 in HCCLM6 cells reduced HCCLM6 growth in vivo.
  
  
  CONCLUSIONS
  Our data demonstrate that ARNT2 plays an inhibitory role in HCC progression and suggest that ARNT2 may be a potential prognostic predictor and therapeutic target for HCC.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.forename: Biwei
authors.initials: B
authors.lastname: Yang
authors.forename: Huichuan
authors.initials: H
authors.lastname: Sun
authors.forename: Weizhong
authors.initials: W
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D005544:Forecasting; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; C490989:ARNT2 protein, human
keywords: ARNT; ARNT2; hepatocellular carcinoma; prognosis; tumor growth