RNA binding protein Nova1 promotes tumor growth in vivo and its potential mechanism as an oncogene may due to its interaction with GABA(A) Receptor-γ2

BACKGROUND: The mechanism of Nova1’s role in hepatocellular carcinoma has not been delineated. Also its interaction with GABA(A) receptor γ2 in HCC is unveiled. This study is aimed to make it clear the distribution, prognostic value of GABA(A)Rγ2 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 GABA(A)Rγ2 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 GABA(A)Rγ2 in HCC tissue. RESULTS: Immunohistochemical staining showed GABA(A)Rγ2 expression in HCC. Survival analysis showed intratumoral GABA(A)Rγ2 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 GABA(A)Rγ2 and GABA. Protein level interaction of GABA(A)Rγ2 and Nova-1 was evidenced by co-immunoprecipitation. CONCLUSIONS: Nova1 interacts with GABA(A)Rγ2 not only in CNS but also in HCC. Nova1’s potential mechanism as an oncogene may due to its interaction with GABA(A) Rγ2. A better understanding of the mechanism of Nova1 for HCC progression provides a novel target for an optimal immunotherapy against this fatal malignancy.