The investigation of possible interactions between ARİD3A, PTEN and AKI1 in osteosarcoma

One of the most common malignant tumor is osteosarcoma in children. Effective treatment strategies are needed to inhibit local tumor growth and tumor cells' metastasis to different tissues and to improve patient survival rates. To find out the molecules and their signaling mechanisms involved in the tumor development and tumor cell migration are of key importance for improving new and effective therapeutic approaches. ARID3A/DRIL1/Bright is a member of the AT rich interaction domain (ARID) DNA-binding proteins that are involved in different biological processes. The serine/threonine kinase AKT1, is a proto-oncogene, has become an important point due to its critical role in metabolism, growth, proliferation, survival, transcription and protein synthesis. In addition, tumor suppressor phosphatase and tensin homolog (PTEN) negatively regulates Akt activation by preventing its phosphorylation. In this thesis, we hypothesized that ARID3A might have an interaction and functional connection with AKT1 and PTEN in osteosarcoma. Silencing and overexpression of ARID3A in osteosarcoma cell line (U2OS) was demonstrated. We noticed that silencing and overexpression of ARID3A decreased and increased the expression of AKT1 respectively in osteosarcoma. However, the silencing and overexpression of ARID3A had no impact on PTEN. The obtained results indicate that ARID3A regulates AKT1 directly in osteosarcoma. Our study has given one more option in the treatment of osteosarcoma by targeting AKT1 via ARID3A. Thus we hope that ARID3A can be used as a therapeutic target in osteosarcoma as it controls the expression of AKT1 directly. Keywords: AKT1, ARID3A, Osteosarcoma, Overexpression, PTEN, Silencing.