Nova1 Promotes The Occurrence And Development Of Melanoma By Regulating The Expression Of FoxO3a

Background Melanoma is derived from melanocytes and responsible for most of skin tumor-related deaths in human.Increasing studies have suggested that dysregulation of RNA binding proteins(RBPs)contributes to cancer progression.Neuro-oncological ventral antigen 1(Nova 1)is a novel RBP and plays an important role in tumor development.Noval is expressed in central nervous system and can bind to the YCAY motif through its KH domain,thereby modulating alternative splicing.However,the expression and role of Noval in melanoma remain unknown.ObjectiveIn this study,we firstly detected the expression of Noval in cutaneous melanoma tissues and benign nevus tissues.Then,we investigated the role of Noval in melanoma cell.Furthermore,we explored the potential mechanism of Noval in melanoma.MethodPart one:Immunohistochemical examination of Noval expression in cutaneous melanoma and pigmented nevus.Moreover,RNA and tissue protein were extracted from the cutaneous melanoma and nevus tissue and the expression of Noval was verified by qRT-PCR and Western blot.Part two:We used the small interference RNA(siRNA)to downregulate the expression of Noval and then carried out a variety of cell function experiments in vitro.The tests included Cell Counting Kit-8(CCK-8)test to detect cell proliferation,cell scratch test to detect cell migration ability,Transwell method to detect cell invasion.Part three:To explore the molecular mechanism of Noval in the proliferation,migration and invasion of melanoma cells,Western blot was used to detect the expression of FoxO3a,the key molecule of Akt pathway,as well as its effect on melanoma cell proliferation and apoptosis.ResultsWe indicated that Nova1 expression was upregulated in cutaneous melanoma samples and cell lines.Moreover,we demonstrated that knockdown of Nova1 suppressed melanoma cell proliferation,migration and invasion in both A375 and A875 cell lines.In addition,we showed that suppressed expression of Noval enhanced forkhead box O3a(FoxO3a)expression while inhibited AKT expression in melanoma cell.Furthermore,we demonstrated that inhibited expression of FoxO3a rescued Nova1-mediated cell proliferation,migration and invasion in melanoma cell line A375.Conclusion:These results suggested that Nova1 acted as an oncogene in the development of melanoma partly through regulating FoxO3a expression.