Ninawe Anupama, Guru Sameer Ahmad, Yadav Prasant, Masroor Mirza, Samadhiya Amit, Bhutani Namrata, Gupta Naresh, Gupta Richa, Saxena Alpana
Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi 110002, India.
Department of Medicine, Maulana Azad Medical College and Associated Hospitals, New Delhi 110002, India.
ACS Omega. 2021 Mar 15;6(11):7711-7718. doi: 10.1021/acsomega.1c00035. eCollection 2021 Mar 23.
MicroRNA miR-486-5p has been reported as a potential biomarker for diagnosis, prognosis, and as a therapeutic target in various cancers. In this study, we analyzed alterations in the expression of miR-486-5p in chronic Myeloid Leukemia (CML) patients. Initially, the expression of miR-486-5p was studied in the BCR-ABL1+ve CML K562 cell line by quantitative real-time polymerase chain reaction (qRT-PCR). The results indicated that the miR-486-5p expression was significantly upregulated in K562 cells after imatinib exposure, as compared to untreated K562 cells (-value = 0.047). These observations were corroborated by a hospital-based study of the miR-486-5p expression in peripheral blood leucocytes of 36 CML patients in the chronic phase (CP) and compared with age and sex-matched healthy volunteers as control subjects. qRT-PCR-based quantification revealed significant downregulation of the miR-486-5p expression in newly diagnosed untreated CP-CML patients' samples (2 = 13.19 ± 14.41) as compared to control samples (2 = 254.5 ± 274.8) (-value < 0.0001). Levels of miR-486-5p were found to be distinctly elevated in the post-imatinib treatment samples of CML patients (2 = 469.7 ± 312.9) as compared to pre-treatment samples (-value < 0.0001). CML patients' clinical and hematological responses to imatinib therapy (oral dose of 400 mg OD) were monitored for 12 months. The correlation of pre-treatment miR-486-5p levels with Sokal score indicated that patients with a higher expression of miR-486-5p had better prognoses. Patients with higher pre-imatinib miR-486-5p levels also showed a major hematologic response to imatinib in a shorter time and . To the best of our knowledge, this is the first report of alterations in the miR-486-5p expression in peripheral blood leucocytes of CML patients. Our observations support a tumor suppressor role of miR-486-5p in CML. The downregulation of the miR-486-5p expression may be critically important in the disease progression of CML patients. The upregulation of the miR-486-5p expression in post-imatinib exposure K562 cells and CML patients after 12 months of imatinib treatment suggests an onco-suppressor effector role of miR-486-5p in the BCR-ABL downstream signaling pathway. miR-486-5p can be explored as a novel biomarker for the early detection of CML.
据报道，微小RNA miR-486-5p可作为多种癌症诊断、预后评估的潜在生物标志物及治疗靶点。在本研究中，我们分析了慢性髓系白血病（CML）患者中miR-486-5p表达的变化。首先，通过定量实时聚合酶链反应（qRT-PCR）研究了miR-486-5p在BCR-ABL1阳性的CML K562细胞系中的表达。结果表明，与未处理的K562细胞相比，伊马替尼处理后的K562细胞中miR-486-5p表达显著上调（P值 = 0.047）。一项基于医院的研究对36例慢性期（CP）CML患者外周血白细胞中miR-486-5p的表达进行了检测，并与年龄和性别匹配的健康志愿者作为对照进行比较，证实了上述观察结果。基于qRT-PCR的定量分析显示，新诊断未治疗的CP-CML患者样本中miR-486-5p表达显著下调（2 = 13.19 ± 14.41），而对照样本中为（2 = 254.5 ± 274.8）（P值 < 0.0001）。与治疗前样本相比，CML患者伊马替尼治疗后样本中miR-486-5p水平明显升高（2 = 469.7 ± 312.9）（P值 < 0.0001）。对CML患者接受伊马替尼治疗（口服剂量400 mg OD）的临床和血液学反应进行了12个月的监测。治疗前miR-486-5p水平与Sokal评分的相关性表明，miR-486-5p表达较高的患者预后较好。伊马替尼治疗前miR-486-5p水平较高的患者对伊马替尼的主要血液学反应出现时间也更短。据我们所知，这是关于CML患者外周血白细胞中miR-486-5p表达变化的首次报道。我们的观察结果支持miR-486-5p在CML中发挥肿瘤抑制作用。miR-486-5p表达的下调可能在CML患者的疾病进展中起关键作用。伊马替尼处理后的K562细胞以及伊马替尼治疗12个月后的CML患者中miR-486-5p表达上调，表明miR-486-5p在BCR-ABL下游信号通路中发挥肿瘤抑制效应作用。miR-486-5p可作为早期检测CML的新型生物标志物进行探索。
