Identification of the roles of miR-363-3p and miR-200c-3p in human head and neck squamous cell carcinomas

Head and neck cancers (HNC) are the sixth most common malignancy. Despite significant advances in the diagnosis and treatment, HNCs are still one of the major causes of cancer-related deaths. The expectation that the mortality and incidence of HNC will increase worldwide has revealed the necessity for development of new treatment approaches. It has become a necessity to discover important biomarkers in order to advance the development of new treatment methods. In this thesis, it is aimed to better understand the in vitro roles of miR-200c-3p/miR-363-3p in the pathogenesis of HNC, to identify possible new target genes and to understand the contribution of this target to the HNC pathogenesis Although miR-200c-3p expression was found to be decreased in HNC tumor tissues compared to normal tissue samples, it was determined that miR-363-3p expression did not change in tumor samples compared to normal tissue samples. Considering these findings, the possible tumor suppressor potential of miR-200c-3p was investigated in subsequent functional studies. The effects of ectopic overexpression of miR-200c-3p on cancer-related phenotypes of HNC cells, such as cell viability, cell migration, cell invasion and cell apoptosis were investigated by a number of in vitro tests. In addition, SSFA2 which was identified as a candidate target gene with the help of in silico analyzes, was confirmed as a direct target of miR-200c-3p for the first time in this thesis. In addition, a number of in vitro tests revealed that SSFA2 has oncogenic potential in the pathogenesis of HNC. In addition, we demonstrated that SSFA2 is overexpressed in taxol resistant cells and along with downregulation of IP3R1, the Ca2+ release channel. Our findings revealed that miR-200c-3p/SSFA2/IP3R1 axis may contribute to HNC pathogenesis and development of taxol resistance and SSFA2 may serve as an important therapeutic target to overcome taxol resistance in HNCs.