Pankreas Kanseri Hücre Hattında TFAM Ekspresyon Düzeyinin Hücre Fonksiyonları Üzerine Etkisi
Narin Şimşek, Ceren
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Pancreatic cancer is an aggressive malignancy with a poor prognosis. Early diagnosis and application of tumor-specific treatment are very important in pancreatic cancer. Therefore, new biomarkers are needed in the diagnosis and treatment of tumors. Micro RNAs (miRNAs), also known as non-protein-coding RNAs, are endogenous RNAs targeted as cancer biomarkers. miRNAs cause low specificity binding of the target gene to messenger RNAs (mRNA), mRNA degradation and translational inhibition, and play important roles in the control of gene expression. In this study, the relationship between miR-200a-3p, which acts as a tumor suppressor, and one of its target genes, Mitochondrial Transcription Factor A (TFAM), was examined at the gene expression level. TFAM is considered a binding chaperone in packaging nucleotides of mitochondrial DNA (mtDNA) and is required for mtDNA replication and transcription. It is known that the TFAM gene is overexpressed in many tumors and shows oncogene character. In our study, miR-200a-3p gene expression was increased by mimic transfection in Panc-1 and Miapaca-2 pancreatic cancer cell lines with low miR-200a-3p gene expression levels. It was shown that TFAM gene expression, which is highly expressed in pancreatic cancer cell lines, decreased with the increase of miR-200a-3p gene expression. It was found that there was a negative correlation between increased miR-200a-3p gene expression and cell viability and a positive correlation between late apoptosis. As a result of mimic miR-200a-3p transfection, its proliferation in the Panc-1 cell line was found to be decreased. These findings showed that TFAM, which is one of its target genes and associated with poor prognosis, is regulated at the transcriptional levels by modulation of miR-200a-3p expression in pancreatic cancer as a result of mimic or inhibitor application and miR-200a-3p can be a target biomarker.