Comparative analysis of miRNA expression levels in prostate cancer patients

MicroRNAs (miRs) take part in modulating the expression of target genes in the signal pathway on transcriptome level in carcinogenesis. In this thesis firstly, the expression level of epi-miRNAs, which be a new miRNA class and evaluating as clinicopathologically in prostate cancer (PCa) were investigated by quantitative real-time PCR method. Then, promoter methylation levels of 11 epi-miRNAs, whose expression levels were found to be significantly higher, were examined by methylation-specific quantitative real-time PCR method. According to the results, hypomethylation was found in the promoter regions of miRNAs that showed a direct proportional increase with PSA levels (miR-34b/c, miR-148a, miR-152), GS's (miR-34a-5p, miR-34b/c, miR-101-2, miR-126, miR-148a, miR- 152, miR-185-5p) and T staging (miR-34a-5p, miR-34b/c, miR-101-2, miR-126, miR-140, miR-148a, miR-152, miR-185-5p). When miR-200a/b was evaluated according to clinicopathological parameters, it acted as an onco-miR in local/local advanced PCa and as a tumor-suppressor-miR in the metastatic stage. In the next stage, the ''epi-miRNA-mRNA'' regulatory network was investigated between miR-34b, miR-34c, miR-148a, miR-152, miR200a, miR-200b epi-miRNAs that was found up-regulated (miR-200a and b were identified as down-regulated at the metastatic stage) and their target genes (DNMT1, 3a, 3b, PTEN and NKX3.1) in PCa. it has been shown that miR-148a, miR-152 and miR-200b increase the expression of DNMT1 and suppress the PTEN gene. it has been emphasized the "epi-miRNA-mRNA" bidirectional feedback loop and highlighted the methylation pattern in PCa anti-cancer therapeutics. It is a new, pioneer and crucial thesis in that it draws attention to the integrative analysis of the mRNA-miRNA expression profiles of miRNAs, methylation process and genes involved in this process as diagnostic and prognostic biomarkers in PCa.