Background

MicroRNAs (miRNAs) function as post-transcriptional mediators for genes involved in cancer progression, including chronic lymphocytic leukemia. MiR-582-5p has been identified as a tumor suppressor in various tumors. The antioncogenic role of miR-582-5p was then validated in this study.

Objective

Mononuclear cells were isolated from peripheral blood samples of patients with chronic lymphocytic leukemia and healthy donors. Expression of miR-582-3p in the mononuclear cells was examined by qRT-PCR. CCK8 assay was performed to detect cell viability, and cell cycle and apoptosis were evaluated by flow cytometry. Dual luciferase activity assay was performed to determine the targeting relationship between miR-582-3p and HNRNPA1, and western blot was performed to unravel the mechanism.

Results

MiR-582-5p was reduced in mononuclear cells of patients with chronic lymphocytic leukemia compared to healthy donors. Forced miR-582-5p expression reduced cell viability, and promoted apoptosis of chronic lymphocytic leukemia cells. Cell cycle was arrested in G0/G1 phase via miR-582-5p mimic. MiR-582-5p bound to HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1) and down-regulated its expression. Silence of HNRNPA1 decreased cell viability, promoted apoptosis, and blocked cell cycle at G0/G1 phase through up-regulation of IκBα (IkappaBalpha). Moreover, HNRNPA1 silencing attenuated the promotive effect induced by miR-582-5p inhibitor on the progression of chronic lymphocytic leukemia.

Conclusion

MiR-582-5p demonstrated anti-proliferative and pro-apoptotic roles in chronic lymphocytic leukemia cell growth via down-regulation of HNRNPA1 and up-regulation of IκBα, thus inactivating NF-κB.

中文翻译：

---

miR-582-5p通过靶向HNRNPA1和抑制NF-κB在慢性淋巴细胞白血病中的抗增殖和促凋亡作用

背景

MicroRNA (miRNA) 作为参与癌症进展的基因的转录后介质，包括慢性淋巴细胞白血病。MiR-582-5p 已被鉴定为各种肿瘤中的肿瘤抑制因子。然后在本研究中验证了 miR-582-5p 的抗癌作用。

客观的

从慢性淋巴细胞白血病患者和健康供体的外周血样本中分离出单核细胞。通过qRT-PCR检测单核细胞中miR-582-3p的表达。进行CCK8测定以检测细胞活力，并通过流式细胞术评估细胞周期和细胞凋亡。进行双荧光素酶活性测定以确定 miR-582-3p 和 HNRNPA1 之间的靶向关系，并进行蛋白质印迹以解开该机制。

结果

与健康供体相比，慢性淋巴细胞白血病患者的单核细胞中的 MiR-582-5p 减少。强制 miR-582-5p 表达降低了细胞活力，并促进了慢性淋巴细胞白血病细胞的凋亡。细胞周期通过 miR-582-5p 模拟物在 G0/G1 期停滞。MiR-582-5p 与 HNRNPA1（异质核核糖核蛋白 A1）结合并下调其表达。HNRNPA1 的沉默通过 IκBα (IkappaBalpha) 的上调降低了细胞活力，促进了细胞凋亡，并在 G0/G1 期阻断了细胞周期。此外，HNRNPA1 沉默减弱了 miR-582-5p 抑制剂对慢性淋巴细胞白血病进展的促进作用。

结论

MiR-582-5p 通过下调 HNRNPA1 和上调 IκBα，从而使 NF-κB 失活，在慢性淋巴细胞白血病细胞生长中表现出抗增殖和促凋亡作用。