Yilmaz Asu Fergün, Kaymaz Burçin, Aktan Çağdaş, Soyer Nur, Kosova Buket, Güneş Ajda, Şahin Fahri, Cömert Melda, Saydam Güray, Vural Filiz
Department of Hematology, İzmir Kâtip Çelebi University Atatürk Training and Research Hospital , İzmir , Turkey.
Department of Medical Biology, Ege University Hospital , İzmir , Turkey.
Turk J Biol. 2017 Dec 18;41(6):926-934. doi: 10.3906/biy-1705-66. eCollection 2017.
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.
在酪氨酸激酶抑制剂时代,耐药性仍是慢性髓性白血病(CML)患者面临的一个问题;因此,像微小RNA(miRNAs)这样的新的通路特异性抑制剂在难治性患者的治疗中变得至关重要。关于靶向信号转导和转录激活因子5A(STAT5A)和5B的miRNAs及抗miRNA治疗,目前尚无令人满意的数据。在本研究中,我们首先研究了达沙替尼对CML细胞系K562凋亡的影响。然后确定了可能同时靶向STAT5A和5B的miRNAs的表达情况。使用ΔΔCT法比较了这些miRNAs的下调和上调情况。在研究的最后阶段,我们使用了一种新的引物探针来验证结果。与对照组相比,达沙替尼治疗组中hsa-miR-940的水平降低了4.4倍,hsa-miR-527和hsa-miR-518a-5p的水平分别升高了12.1倍和8倍。在验证步骤中我们检测到了类似的结果。总之,我们确定了在CML发病机制中起重要作用的靶向STAT5A和5B的miRNAs的表达谱。所获得的数据可能有助于确定CML患者的新治疗靶点。