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Down-regulation of Musashi-2 exerts antileukemic effects on acute lymphoblastic leukemia cells and increases sensitivity to dexamethasone

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Abstract

Musashi-2 (MSI2), implicated in the oncogenesis and propagation of a broad array of malignancies, inclusive of certain leukemia, remains a nascent field of study within the context of acute lymphoblastic leukemia (ALL). Using lentiviral transfection, ALL cells with stable MSI2 knockdown were engineered. A suite of analytic techniques – a CCK-8 assay, flow cytometry, qRT-PCR, and western blotting – were employed to evaluate cellular proliferation, cell cycle arrest, and apoptosis and to confirm differential gene expression. The suppression of MSI2 expression yielded significant results: inhibition of cell proliferation, G0/G1 cell cycle arrest, and induced apoptosis in ALL cell lines. Furthermore, it was noted that MSI2 inhibition heightened the responsiveness of ALL cells to dexamethasone. Significantly, the depletion of MSI2 prompted the translocation of GR from the cytoplasm to the nucleus upon dexamethasone treatment, consequently leading to enhanced sensitivity. Additionally, the FOXO1/4 signaling pathway contributed to the biological effects of ALL cells evoked by MSI2 silencing. Our study offers novel insight into the inhibitory effects of MSI2 suppression on ALL cells, positing MSI2 as a promising therapeutic target in the treatment of ALL.

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The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author.

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Funding

This work garnered support from the Medical and Health Science and Technology Projects of Zhejiang Province (Grant Numbers: 2019KY170 and 2023KY1050), the Natural Science Foundation of Ningbo (Grant Number: 2022J208), and partially from the Zhejiang Provincial Natural Science Foundation of China (Grant Number: LY20H080001).

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Authors and Affiliations

  1. Laboratory of Stem Cell Transplantation, Ningbo First Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China

    Duobing Zou, Ying Chen, Tingting Niu, Chao Ma, Cong Shi, Zhenya Huang, Ying Wu, Yun Wang, Ningning Wu, Yi Zhang & Qitian Mu

  2. Department of Hematology, Ningbo Chinese Medical Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China

    Mei Lv

  3. Department of Hematology, Ningbo First Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China

    Shujun Yang & Guifang Ouyang

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  1. Duobing Zou
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  2. Mei Lv
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  4. Tingting Niu
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  12. Yi Zhang
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  13. Guifang Ouyang
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  14. Qitian Mu
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Contributions

D Zou and M Lv performed the majority of the experiments, while Y Wu, Z Huang, and C Ma contributed to a portion of the experimental procedures. C Shi, Y Wang, and S Yang conducted the experimental analysis. T Niu and Y Chen performed statistical analysis. Q Mu and G Ouyang conceptualized the study and also assisted in manuscript composition. D Zou primarily drafted the manuscript, while Y Zhang and N Wu undertook editorial duties. All authors have read and given their approval to the final manuscript.

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Correspondence to Guifang Ouyang or Qitian Mu.

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Zou, D., Lv, M., Chen, Y. et al. Down-regulation of Musashi-2 exerts antileukemic effects on acute lymphoblastic leukemia cells and increases sensitivity to dexamethasone. Ann Hematol 103, 141–151 (2024). https://doi.org/10.1007/s00277-023-05468-z

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