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MicroRNA-153-3p enhances the sensitivity of chronic myeloid leukemia cells to imatinib by inhibiting B-cell lymphoma-2-mediated autophagy

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Abstract

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease caused by abnormal DNA replication of bone marrow stem cells and chemotherapy resistance is a major obstacle to the effective treatment of patients with CML. Imatinib (IM), a tyrosine kinase inhibitor (TKI), is a first-line drug clinically used for CML. Mounting evidence has indicated that the dysregulation of microRNAs (miRNAs) is associated with the chemoresistance of CML. In this study, miR-153-3p, which had been implicated with numerous types of tumors, was identified to be downregulated in IM-resistant CML cells. Upregulation of miR-153-3p significantly increased IM sensitivity and decreased the survival rate of IM-resistant CML cells, whereas downregulation of miR-153-3p attenuated these effects in IM-resistant CML cells. Upregulated miR-153-3p could decrease the autophagy caused by IM in IM-resistant CML cells. Dual-luciferase reporter assays confirmed that Bcl-2 is a direct target of miR-153-3p. Bcl-2 restoration reversed the increased sensitivity to IM induced by miR-153-3p-mimic transfection in IM-resistant CML cells. The results of the present study showed that dysregulated miR-153-3p may target Bcl-2 to promote the development of IM resistance and attenuate IM-induced apoptosis in CML. Therefore, miR-153-3p upregulation combined with IM treatment may serve as a promising therapeutic strategy for patients with low sensitivity.

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Availability of data and material

The datasets used and/or analyzed in the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the scientific and innovative strategic special fund of Guangdong province (2018A030310299), doctor initiating scientific project of The Third Affiliated Hospital of Guangzhou Medical University (2017B07), and elite personnel project of The Third Affiliated Hospital of Guangzhou Medical University (2018001).

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Authors and Affiliations

  1. Department of Hematology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China

    Yu-Ling Li, Jia-Ming Tang, Xiao-Yun Chen, Bing Luo, Guo-Hua Liang, Qian Qu & Zi-Yuan Lu

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  1. Yu-Ling Li
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  2. Jia-Ming Tang
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  3. Xiao-Yun Chen
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  4. Bing Luo
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  7. Zi-Yuan Lu
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Contributions

Z-YL and Y-LL designed the research. Y-LL, Z-YL, J-MT, X-YC and BL performed the experiments, analyzed the data, and wrote the paper. G-HL performed the cell culture experiments. QQ collected the data and performed the statistical analyses.

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Correspondence to Zi-Yuan Lu.

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The authors declare that they have no conflict of interest.

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All human blood samples investigated in this study were in accordance with the ethical standards of the Ethics Committee of The Third Affiliated Hospital of Guangzhou Medical University, and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual sample donor included in the study.

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Li, YL., Tang, JM., Chen, XY. et al. MicroRNA-153-3p enhances the sensitivity of chronic myeloid leukemia cells to imatinib by inhibiting B-cell lymphoma-2-mediated autophagy. Human Cell 33, 610–618 (2020). https://doi.org/10.1007/s13577-020-00367-1

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  • DOI: https://doi.org/10.1007/s13577-020-00367-1

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