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Determining expression of miRNAs that potentially regulate STAT5A and 5B in dasatinib-sensitive K562 cells

机译:确定在dasatinib敏感的K562细胞中可能调节STAT5A和5B的miRNA的表达

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摘要

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.
机译:在酪氨酸激酶抑制剂时代,抗药性仍然是慢性粒细胞白血病(CML)患者的一个问题。因此,新的途径特异性抑制剂(如miRNA)在难治性患者的治疗中已变得重要。关于针对STAT5A和5B的miRNA和抗miRNA治疗,尚无令人满意的数据。在这项研究中,我们首先研究了达沙替尼对CML细胞K562细胞凋亡的影响。然后确定可能靶向STAT5A和5B的miRNA的表达。使用ΔΔCT方法比较了miRNA的下调和上调。在研究的最后阶段,我们使用了新的引物探针以验证结果。与对照组相比,达沙替尼治疗组的hsa-miR-940水平降低了4.4倍,hsa-miR-527和hsa-miR-518a-5p水平分别提高了12.1和8倍。 。我们在验证步骤中检测到了相似的结果。结论是,我们确定了针对STAT5A和5B的miRNA的表达谱,这些表达在CML的发病机理中具有重要作用。获得的数据可能会为CML患者确定新的治疗目标。

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