title: RNA binding protein Nova1 promotes tumor growth in vivo and its potential mechanism as an oncogene may due to its interaction with GABAAReceptor-γ2.
abstract: BACKGROUND
  The mechanism of Nova1's role in hepatocellular carcinoma has not been delineated. Also its interaction with GABAAreceptor γ2 in HCC is unveiled. This study is aimed to make it clear the distribution, prognostic value of GABAARγ2 in human hepatocellular carcinoma. And its role in HCC tumorigenesis under the regulation of its alternative splicing factor Nova1.
  
  
  METHODS
  Immunohistochemistry staining was used to investigate the distribution and clinical significance of GABAARγ2 protein expression in hepatocellular carcinoma. In vivo tumorigenticity test was conducted in nude mice by regulation the expression of Nova1. Later, western blot and co-immunoprecipitation were carried out to verify the interaction between Nova1 and GABAARγ2 in HCC tissue.
  
  
  RESULTS
  Immunohistochemical staining showed GABAARγ2 expression in HCC. Survival analysis showed intratumoral GABAARγ2 was an independent prognostic factor for overall survival (OS) and disease free survival (DFS). Up-regulation of Nova1 expression promotes subcutaneous HCC growth in nude mice and western blot showed the ectopic expression of Nova-1 restro-regulates the expression of GABAARγ2 and GABA. Protein level interaction of GABAARγ2 and Nova-1 was evidenced by co-immunoprecipitation.
  
  
  CONCLUSIONS
  Nova1 interacts with GABAARγ2 not only in CNS but also in HCC. Nova1's potential mechanism as an oncogene may due to its interaction with GABAARγ2. A better understanding of the mechanism of Nova1 for HCC progression provides a novel target for an optimal immunotherapy against this fatal malignancy.
authors.affiliation: Department of Hematology, Zhongshan Hospital of Fudan University, Zhongshan Hospital, No.180 Fenglin Road Xuhui District, Shanghai, China.
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Zhongshan Hospital, No.180 Fenglin Road Xuhui District, Shanghai, China.
authors.forename: Hai-Ning
authors.initials: HN
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Zhongshan Hospital, No.180 Fenglin Road Xuhui District, Shanghai, China.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Zhongshan Hospital, No.180 Fenglin Road Xuhui District, Shanghai, China.
authors.forename: Dan-Ying
authors.initials: DY
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Zhongshan Hospital, No.180 Fenglin Road Xuhui District, Shanghai, China.|Key Laboratory of Medical Molecule Virology, Ministry of Education and Health, Shanghai Institute of Liver Diseases, Zhongshan Hospital, No.180 Fenglin Road Xuhui District, Shanghai, China.
authors.forename: Xi-Zhong
authors.initials: XZ
authors.lastname: Shen
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Zhongshan Hospital, No.180 Fenglin Road Xuhui District, Shanghai, China. liu.taotao@zs-hospital.sh.cn.
authors.forename: Tao-Tao
authors.initials: TT
authors.lastname: Liu
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics*; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000090682:Neuro-Oncological Ventral Antigen; D009857:Oncogenes; D009928:Organ Specificity; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism
chemical_list: C000594513:NOVA1 protein, human; D000090682:Neuro-Oncological Ventral Antigen; D016601:RNA-Binding Proteins; D011963:Receptors, GABA-A
keywords: GABAA Receptor-γ2; Nova1; Oncogene; RNA binding protein