ARID3A regulates autophagy related gene BECN1 expression and inhibits proliferation of osteosarcoma cells

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor which has unclear pathobiology. Hence, enlightening the exact molecular mechanism underlying osteosarcoma progression is crucial for developing new treatment strategies. One member of the ARID family of DNA binding proteins is ARID3A that is implicated in osteosarcoma pathogenesis. ARID3A could bind E2F1 and regulate the transcription of E2F1 targets. At the same time, BECN1 is a well-characterized autophagy regulator gene that is a direct target of E2F1. The present study aimed to investigate the effect of ARID3A on the expression of BECN1 in osteosarcoma cells. First, we determined gene expression levels of ARID3A, BECN1, and E2F1 in U-2 OS by qPCR and confirmed with online datasets from GEO database. In addition, the prognostic value of these genes was also evaluated from Kaplan-Meier plotter database. Next, ARID3A was overexpressed and silenced in order to investigate the effect of ARID3A on BECN1 expression and proliferation of U-2 OS cells. Our results demonstrated that BECN1 was negatively correlated with E2F1 and positively correlated with ARID3A based on initial expression and prognostic effect in OS. Overexpression of ARID3A upregulated BECN1 while silenced ARID3A downregulated BECN1 expression in U-2 OS cells. Additionally, silencing of ARID3A promoted colony formation and proliferation, whereas overexpression of ARID3A suppressed colony formation and proliferation of U-2 OS cells. Taken together, these results indicate that ARID3A could function as tumor suppressor and affect the expression level of BECN1 in U-2 OS cells.