RNA binding protein Nova1 promotes tumor growth in vivo and its potential mechanism as an oncogene may due to its interaction with GABAA 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_ARγ2 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_ARγ2 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_ARγ2 in HCC tissue. Results: Immunohistochemical staining showed GABAARγ2 expression in HCC. Survival analysis showed intratumoral GABA_ARγ2 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_ARγ2 and GABA. Protein level interaction of GABA_ARγ2 and Nova-1 was evidenced by co-immunoprecipitation. Conclusions: Nova1 interacts with GABA_ARγ2 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. [ABSTRACT FROM AUTHOR]