Identification of Circular RNAs as Biomarker Candidates in Lung Cancer
Project no. 22814 · Status: Kapanmış · 2021
Summary
Lung cancer is the most common malignancy and among the leading cause of cancer death worldwide. Currently, a multimodal approach is used in the treatment of lung cancer with combinations of surgery, radiotherapy and chemotherapy regimens. The fact that cancer has a complex mechanism causes inadequacies and difficulties both in the diagnosis of the disease and the management of treatment. Therefore, there is an important need for biomarkers that can be used in the early diagnosis of the disease and in the follow-up of treatment. Circular RNAs (circRNAs) play an important role in regulation of gene expression and development of biological mechanism. In addition, circRNAs have a covalently closed circular structure that lacks 3' and 5' polar ends and is resistant to RNAase enzymes. Due to these properties, they can be found stably in body tissues and fluids. Therefore, they can be potential biomarkers in the diagnosis, monitoring of therapeutic response and prognosis of cancer. In our thesis study, it was aimed to investigate the expression levels of circRNA molecules in the treatment of lung cancer and to determine those that have the potential to be biomarkers. For this, non-small cell lung cancer cell line, A549 cells, were used. The expression levels of 169 circRNAs and the changes in these levels were investigated by applying carboplatin and pemetrexed treatment in this cell line. First, cytotoxicity tests of these drugs were performed and IC50 values were determined, and individual and combined treatments were applied in the A549 cell line. Total RNA isolation and cDNA synthesis were performed from the cells obtained after drug administration. Expression levels of circRNA genes were determined by RT-qPCR method with the designed primer sequences. As a result, while carboplatin, pemetrexed, and combined drug applications changed the expression levels of some circRNAs in lung cancer cells, some circRNAs were expressed only after treatment. In treatment follow-up and management, some circRNAs have been identified as potential biomarker candidates. Further studies on these circRNA candidates need to be performed and supported by in vivo and human studies.