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Anti-proliferation and pro-apoptosis effects of miR-582-5p in chronic lymphocytic leukemia via targeting HNRNPA1 and suppression of NF-κB

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Abstract

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.

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Authors and Affiliations

  1. Department of Hematology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Ürümqi City, 830001, China

    Zengsheng Wang, Yan Li, Tao Lang, Min Mao & Xiaoyan Zhang

  2. Department of Hematology, Eastern Hospital, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, No. 585, Honghe North Road, Damian street, Longquanyi District, Chengdu City, 610101, Sichuan Province, China

    Xiaochuan Kuang & Haiqing Yang

  3. Department of Obstetrics and Gynecology, The Sixth People’s Hospital of Chengdu, Chengdu City, 610000, Sichuan Province, China

    Fang Guo

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  1. Zengsheng Wang
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  2. Yan Li
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  3. Xiaochuan Kuang
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  4. Fang Guo
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  5. Tao Lang
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  6. Min Mao
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  7. Xiaoyan Zhang
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  8. Haiqing Yang
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Contributions

ZW and YL designed the study and supervised the data collection; XK analyzed the data and interpreted the data; FG, TL, MM, XZ, and HY prepare the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

Corresponding author

Correspondence to Haiqing Yang.

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Conflict of interest

Author Zengsheng Wang has no conflict of interest. Author Yan Li has no conflict of interest. Xiaochuan Kuang has no conflict of interest. Fang Guo has no conflict of interest. Tao Lang has no conflict of interest. Min Mao has no conflict of interest. Xiaoyan Zhang has no conflict of interest. Haiqing Yang has no conflict of interest.

Ethical approval

Ethical approval was obtained from the Ethics Committee of People’s Hospital of Xinjiang Uygur Autonomous Region. (Aprroval No.2016-23).

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13273_2021_143_MOESM1_ESM.jpg

Supplementary file1 Supplemental Figure S1. Protein expression of IκBα was reduced, while HNRNPA1 was enhanced, in patients with chronic lymphocytic leukemia compared to the healthy donors (JPG 88 kb)

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Wang, Z., Li, Y., Kuang, X. et al. Anti-proliferation and pro-apoptosis effects of miR-582-5p in chronic lymphocytic leukemia via targeting HNRNPA1 and suppression of NF-κB. Mol. Cell. Toxicol. 17, 357–365 (2021). https://doi.org/10.1007/s13273-021-00143-8

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