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miR-603 promotes cell proliferation and differentiation by targeting TrkB in acute promyelocytic leukemia

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Abstract

Arsenic trioxide (ATO) treatment effectively prolongs the overall survival of patients with acute promyelocytic leukemia (APL). Mutations in the oncogene PML::RARA were found in patients with ATO-resistant and relapsed APL. However, some relapsed patients do not have such mutations. Here, we performed microarray analysis of samples from newly diagnosed and relapsed APL, and found different microRNA (miRNA) expression patterns between these two groups. Among the differentially expressed miRNAs, miR-603 was expressed at the lowest level in relapsed patients. The expression of miR-603 and its predicted target tropomyosin-related kinase B (TrkB) were determined by PCR and Western blot. Proliferation was measured using an MTT assay, while apoptosis, cell cycle and CD11b expression were analyzed using flow cytometry. In APL patients, the expression of miR-603 was negatively correlated with that of TrkB. miR-603 directly targeted TrkB and downregulated TrkB expression in the APL cell line NB4. miR-603 increased cell proliferation by promoting the differentiation and inhibiting the apoptosis of NB4 cells. This study shows that the miR-603/ TrkB axis may be a potent therapeutic target for relapsed APL.

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Data Availability

The data are available from the corresponding author on reasonable request.

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Funding

This research was supported by the National Natural Science Foundation of China (81903966) and the Science Foundation of the First Affiliated Hospital of Harbin Medical University (2021M02).

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Authors and Affiliations

  1. Department of Hematology, the First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China

    Huibo Li, Jinxiao Hou, Yueyue Fu, Yanqiu Zhao, Jie Liu, Dan Guo, Ruiqi Lei, Yiting Wu, Linqing Tang & Shengjin Fan

  2. Hematology Department, the Second Hospital of Anhui Medical University, Hefei, 230601, Anhui Province, China

    Jinxiao Hou

  3. NHC Key Laboratory of Cell Transplantation, the First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China

    Shengjin Fan

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  1. Huibo Li
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Contributions

Huibo Li conceived, carried out experiments and wrote the paper; Jinxiao Hou analyzed data; Yueyue Fu and Yanqiu Zhao carried out experiments and analyzed the data; Jie Liu and Dan Guo performed the experiments; Ruiqi Lei, Yiting Wu and Linqing Tang performed the experiments. Shengjin Fan conceived the experiments and revised the paper. All authors gave final approval of the submitted and published versions.

Corresponding author

Correspondence to Shengjin Fan.

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All experimental procedures were approved by the First Affiliated Hospital, Harbin Medical University.

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None of the authors have any financial interest related to this work and therefore declare no conflict of interest.

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Li, H., Hou, J., Fu, Y. et al. miR-603 promotes cell proliferation and differentiation by targeting TrkB in acute promyelocytic leukemia. Ann Hematol 102, 3357–3367 (2023). https://doi.org/10.1007/s00277-023-05441-w

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  • DOI: https://doi.org/10.1007/s00277-023-05441-w

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