Bazı mikrorna ve hedef genlerin koloreketal kanser kemodirenci üzerindeki rollerinin araştırılması

Colorectal cancer remains one of the leading causes of cancer-related mortality worldwide, and resistance to chemotherapy continues to limit therapeutic outcomes. This thesis investigates the molecular mechanisms underlying the anticancer effects of two chemotherapeutic agents, docetaxel and lapatinib, and explores their impact on gene and microRNA expression in colorectal cancer cell lines. In the first part of the study, we evaluated the cytotoxic effects of these drugs across different colorectal cancer cell lines and analyzed the expression of key cancer-related genes following treatment. Both agents significantly reduced cell viability in a dose-dependent manner. Gene expression profiling revealed downregulation of genes involved in proliferation, transcriptional regulation, and oncogenesis, alongside upregulation of genes linked to apoptosis and cell cycle arrest. Interestingly, some drug resistance–associated genes were also induced, highlighting potential barriers to sustained therapeutic efficacy. In the second part, we examined the modulation of selected cancer-associated microRNAs in response to docetaxel and lapatinib and investigated the regulatory role of miR-595 on the oncogene E2F7. Treatment altered the expression patterns of several miRNAs in a cell line dependent manner. Notably, miR-595 negatively regulated E2F7 expression, suggesting a functional interaction that may influence chemoresistance. Collectively, these findings provide novel insights into the molecular responses induced by docetaxel and lapatinib and suggest that targeting the miR-595/E2F7 axis could enhance chemotherapy efficacy in colorectal cancer.