Determination of NRF3 and NOTCH-2 receptor-related miRNA34-a in gastric cancer and comparison of the effect of cisplatin and doxorobusin application on gene expression

Gastric cancer is the fourth most common malignancy and is a multifuctorial disease that is second cause of cancer-related deaths after lung cancer. NOTCH signaling cascade is an important signaling pathway in gastric carcinogenesis and controls apoptosis, cell differantiation and proliferation. NRF3 which belongs to CNC family, is thought to provide cancer driver gene function to cells, but its physiological function continues to be investigated. Micro RNAs (miRNA) are small, evolutionarily conserved, non-coding single-stranded RNA molecules of 19 to 25 nucleotidesin length, and in cancer miRNAs can function as oncogenes, tumor suppressors or both tumor suppressors and oncogenes. Doxorobusin; it is an anthracychline group chemotherapeutic agent used in many types of cancer and Cisplatin has been determined to have anti-neoplastic effects on tumor cells and has been used for various types of cancer for many years. Within the scope of this thesis project, it is aimed to determine the relationship between NRF3 and NOTCH-2 gene expressions in gastric cancer for the first time and to investigate the effect of Cisplatin and Doxorobusin administration on NRF3 and NOTCH-2 gene expressions. In addition, miRNA34-a which is known to interact with the NOTCH signaling pathway and the NRF3 gene and has been shown bioinformatically to be a factor for cancer, will be detected and its relationship with NRF3 and NOTCH-2 gene expressions will be determined under the same conditions. The effect of Sisplatin and Doxorobucin on gastric cancer cells was determined by MTT Cell Viability determination and MKN-45 and AGS cell lines were cultured under appropiate conditions and treated with chemotherapy agents. Then, NRF3, NOTCH-2 and miRNA34-a gene expressions were examined by real time quantitative polymerase chain reaction. According to our findings; after both drug applications, NRF3 gene expression decreased except for AGS 72h Cisplatin application; NOTCH-2 gene expression decreased in both cell lines after Doxorobusin application but gene expression inceraased in Cisplatin application but it was not statistically significant; it shows that miRNA34-a gene expression increases for AGS 48h Doxorobusin application. It is thought that increased miRNA34-a gene expression may play a tumor suppressor role on oncogenic NRF3 and NOTCH-2 but further studies are needed to understand the relationship between them. Key Words: Gastric Cancer, miRNA34-a, NOTCH-2, NRF3, Chemotherapy Agents