Investigation of possible relation between arid3a, XAF1 and ZNF313 in osteosarcoma

Osteosarcoma is the most common type of bone cancer in children and adolescents. ARID3A (AT-rich interactive domain 3A) is a DNA binding protein, cooperates with E2F for cell cycle progression and also a direct p53 target gene with a wide range of biological processes. X-Linked Inhibitor of Apoptosis (XIAP)-associated factor 1 (XAF1), which was originally identified as a nuclear protein, is a tumor suppressor gene and is ubiquitously expressed in all normal tissues, but absent or present at very low levels in many human cancers. "Really interesting new gene" (RING) finger protein 114 (ZNF313/RNF114) is a zinc-binding protein encoding gene, which exhibits a frequent genomic amplification in multiple human cancers. ZNF313 is a ubiquitin E3 ligase that has a critical role in the regulation of cell cycle progression, differentiation and senescence. It was initially identified as an XAF1-interacting protein, which upregulates the stability and proapoptotic effect of XAF1. We hypothesized that there might have a possible interaction between ARID3A (which is the functional connector of both Rb/E2F1 and p53 tumor suppressor pathways), XAF1 and ZNF313 in osteosarcoma. Such interaction and their mechanisms has not yet been elucidated. In this study, silencing and overexpression of ARID3A in osteosarcoma cell line U2OS was performed and the RNA levels have been measured by Real-Time Quantitative Reverse Transcription PCR (RT-PCR). We noticed that silencing and overexpression of ARID3A decreased and increased the expression of P53, XAF1 and ZNF313 respectively in osteosarcoma. Our obtained results indicate that ARID3A regulates XAF1 and ZNF313 directly in osteosarcoma. Our study has given one more option in the treatment of osteosarcoma by targeting XAF1 and ZNF313 via ARID3A. Our results suggest that ARID3A may be used as a therapeutic target in osteosarcoma as it regulates the expressions of XAF1 and ZNF313 directly. Therefore, further studies are needed to confirm our findings. Keywords: ARID3A, Osteosarcoma, p53, XAF1, ZNF313