Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran; Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Leuk Res. 2021 Dec;111:106691. doi: 10.1016/j.leukres.2021.106691. Epub 2021 Aug 21.
Leukemia is a malignant and progressive disease of hematopoiesis. The disease arises due to abnormal proliferation and development of white blood cells and their precursors in the blood and bone marrow. Chronic lymphoblastic leukemia (CLL) is a subtype of blood cancers, with the origin of B lymphocytes and the involvement of bone marrow, blood and lymph nodes. MicroRNAs (miRNAs) are small non-coding RNAs with pivotal roles in cellular and molecular processes related to different malignancies, including CLL. In this way, we aimed to evaluate the expression of miR-32-5p, miR-98-5p, and miR-374b-5p in CLL patients. We also investigated the signaling pathways regulated by the studied miRs and also frequently disturbed miRs in CLL.
Blood samples were collected from 32 CLL patients from Kermanshah province, Iran and 34 age and sex-matched healthy individuals. RNA was extracted from PBMCs and then was subjected to cDNA synthesis. Using specifically designed primers and Real-Time PCR method the expression of miRNAs was detected and was statistically analyzed. Using mirPath v.3, systematic pathway enrichment analysis was performed for the three studied miRNAs here along with the frequently disturbed miRNAs in CLL.
The experiments indicated a significant reduction in the expression of all three miRs (p-value<0.0001) in CLL patients compared with healthy individuals. ROC analysis suggested that the three studied miRs can serve as potential biomarkers for early diagnosis of CLL. The in silico analysis suggested proteoglycans in cancer as a pathway regulated by the studied miRs and frequently dysregulated miRs in CLL.
The observed reduction in expression of miR-32-5p, miR-98-5p, and miR-374b-5p in treatment naïve CLL patients here might be suggestive of their modulatory protective role in CLL progression. Moreover, the candidate peripheral miRNAs could potentially serve as diagnostic biomarkers which warrant further investigation in a larger sample size.
白血病是一种恶性的、进行性的造血系统疾病。该病源于血液和骨髓中白细胞及其前体细胞的异常增殖和发育。慢性淋巴细胞白血病（CLL）是一种血液癌，起源于 B 淋巴细胞，并涉及骨髓、血液和淋巴结。微小 RNA（miRNA）是一种小的非编码 RNA，在与不同恶性肿瘤相关的细胞和分子过程中起着关键作用，包括 CLL。因此，我们旨在评估 CLL 患者中 miR-32-5p、miR-98-5p 和 miR-374b-5p 的表达情况。我们还研究了受研究 miR 调节的信号通路以及 CLL 中经常失调的 miR。
从伊朗克尔曼沙阿省的 32 名 CLL 患者和 34 名年龄和性别匹配的健康个体中采集血样。从 PBMC 中提取 RNA，然后进行 cDNA 合成。使用特定设计的引物和实时 PCR 方法检测 miRNA 的表达，并进行统计学分析。使用 mirPath v.3，对三种研究 miRNA 以及 CLL 中经常失调的 miRNA 进行系统的通路富集分析。
实验表明，与健康个体相比，CLL 患者所有三种 miR（p 值<0.0001）的表达均显著降低。ROC 分析表明，三种研究 miRNA 可作为 CLL 早期诊断的潜在生物标志物。计算机分析表明，研究 miRNA 及 CLL 中经常失调的 miRNA 调节的通路为癌症中的蛋白聚糖。
本研究观察到治疗初治 CLL 患者中 miR-32-5p、miR-98-5p 和 miR-374b-5p 的表达降低，提示其在 CLL 进展中可能具有调节保护作用。此外，候选外周 miRNA 可能具有作为诊断生物标志物的潜力，需要在更大的样本量中进一步研究。
