Identification of the roles of miR-1825 in human head and neck squamous cell carcinomas

Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common malignant cancer worldwide. Although the therapeutic modalities currently used for patients with HNSCC improved in recent decades, it is an urgent necessity to understand the pathogenesis of HNSCC, to develop novel treatment strategies and to characterize the oncogenes that are responsible for aggressive HNSCC phenotype. In this thesis study, it was aimed to understand the roles of miR-1825 in the pathogenesis of HNSCC, to identify possible new target genes and investigating the potential roles of HNSCC-derived exosomes on angiogenesis under hypoxic conditions by in vitro and in vivo tests. We examined the impacts of miR-1825 deregulation on the cancer associated phenotypes using in vitro tests evaluating cell viability, clonogenicity, cell migration, invasion, apoptosis and stem cell characteristics. Gene microarray analysis was performed to identify potential targets of miR-1825 in HNSCC cells. It has also been shown using NUDE mice in vivo that ectopic miR-1825 overexpression has a stimulating potential on the tumorigenic capacity of HNSCC cells. In addition, in order to reveal the effects of miR-1825 on the microenvironment in the formation of HNSCC, we showed that the level of miR-1825 increased in cells with HNSCC exposed to hypoxic conditions and in exosomes released from these cells. Our findings, it has been revealed that miR-1825/FREM1 axis plays a mediator role in the development of HNSCC and that exosomal miR-1825 stimulates the formation of angiogenesis by targeting the TSC2/mTOR axis in hypoxic conditions that may occur due to HNSCC formation.