Introduction

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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miR-32、miR-98 和 miR-374 在慢性淋巴细胞白血病中的异常表达谱

介绍

白血病是造血的恶性和进行性疾病。该疾病是由于白细胞及其前体在血液和骨髓中的异常增殖和发育而引起的。慢性淋巴细胞白血病（CLL）是血癌的一种亚型，起源于B淋巴细胞，累及骨髓、血液和淋巴结。微小 RNA (miRNA) 是小的非编码 RNA，在与不同恶性肿瘤（包括 CLL）相关的细胞和分子过程中具有关键作用。

通过这种方式，我们旨在评估 miR-32-5p、miR-98-5p 和 miR-374b-5p 在 CLL 患者中的表达。我们还研究了由所研究的 miR 调节的信号通路，以及 CLL 中经常受到干扰的 miR。

方法

从伊朗克尔曼沙赫省的 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。使用专门设计的引物和实时PCR方法检测miRNA的表达并进行统计分析。使用 mirPath v.3，对这里研究的三种 miRNA 以及 CLL 中经常受到干扰的 miRNA 进行了系统的通路富集分析。

结果

实验表明，与健康个体相比，CLL 患者中所有三种 miR 的表达均显着降低（p 值<0.0001）。ROC 分析表明，三种研究的 miR 可以作为 CLL 早期诊断的潜在生物标志物。计算机分析表明，癌症中的蛋白聚糖是受研究的 miR 调节的途径，并且在 CLL 中经常失调的 miR。

结论

在此处观察到的 miR-32-5p、miR-98-5p 和 miR-374b-5p 在治疗过的 CLL 患者中的表达减少可能暗示它们在 CLL 进展中的调节保护作用。此外，候选外周 miRNA 可能作为诊断生物标志物，需要在更大的样本量中进行进一步研究。