Authors: ASU FERGÜN YILMAZ, BURÇİN KAYMAZ, ÇAĞDAŞ AKTAN, NUR SOYER, BUKET KOSOVA, AJDA GÜNEŞ, FAHRİ ŞAHİN, MELDA ÖZKAN, GÜRAY SAYDAM, FİLİZ VURAL
Abstract: In the era of tyrosine kinase inhibitors, resistance still constitutes a problem in chronic myeloid leukemia (CML) patients; thus, new pathway-specific inhibitors like miRNAs have become important in the treatment of refractory patients. There are no satisfying data regarding the miRNAs and anti-miRNA treatment targeting STAT5A and 5B. In this study, we first researched the effect of dasatinib on apoptosis in the CML cell line K562. The expressions of miRNAs possibly targeting both STAT5A and 5B were then determined. The down- and upregulation of the miRNAs were compared using the ΔΔCT method. At the last stage of the study, we used a new primer probe in order to validate the results. The level of hsa-miR-940 was decreased 4.4 times and the levels of hsa-miR-527 and hsa-miR-518a-5p were increased 12.1 and 8 times, respectively, in the dasatinib-treated group when compared to the control group. We detected similar results in the validation step. As a conclusion, we determined the expression profiles of miRNAs targeting STAT5A and 5B that had an important role in the pathogenesis of CML. The data obtained could lead to determining new therapeutic targets for CML patients.
Keywords: miRNA expressions, STAT5A, STAT5B, chronic myeloid leukemia, dasatinib, K562 cells
Full Text: PDF