TRIM6 silencing for inhibiting growth and angiogenesis of gliomas by regulating VEGFA

Abstract

Gliomas are the highest prevalent primary central nervous system (CNS) cancers with poor overall survival rate. There is an urgent need to conduct more research into molecular therapies targeting critical elements of gliomas. This study herein targeted to assess the impact of tripartite motif protein 6 (TRIM6) on gliomas. Using public databases, we found the increased TRIM6 expression in tissues of glioma which was linked with worst overall survival. Silencing TRIM6 promoted glioma cell proliferation, migration and angiogenesis, suggesting the promoting effects of TRIM6 on gliomas. Knockdown of TRIM6 expression downregulated the expression levels of Forkhead box M1 (FOXM1) and vascular endothelial growth factor A (VEGFA) in glioma cells. Afterwards, impact of TRIM6 on VEGFA expression was regulated by FOXM1. VEGFA overexpression reversed the decreased abilities of glioma cell proliferation, migration and angiogenesis caused by silencing TRIM6. Furthermore, we also found that TRIM6 promoted the growth of gliomas in the xenograft mouse model. In summary, the expression of TRIM6 was increased which was related to poor prognosis of glioma patients. TRIM6 promoted glioma cell proliferation, migration and angiogenesis through the FOXM1-VEGFA pathway. Therefore, TRIM6 carries capacity to be explored as a novel therapeutic target in clinical.

Keywords: Angiogenesis; FOXM1; Glioma; TRIM6; VEGFA.