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MiR-383 sensitizes osteosarcoma cells to bortezomib treatment via down-regulating PSMB5

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Abstract

Background

Proteasome inhibition is a promising strategy for cancer therapy. Bortezomib, which primarily targets the chymotrypsin-like activity of PSMB5, has demonstrated efficacy in various tumors. However, there is variable sensitivity to bortezomib, which could be attributed, in part, to variations in the expression of proteasome subunits.

Methods and results

In this study, we investigated whether miR-383 affects the expression of proteasome subunits in osteosarcoma (OS) cells, and if so, whether OS cells display differential sensitivity to bortezomib concerning miR-383 expression. We detected a decreased miR-383 expression in OS cells and tissues. Then we found a negative correlation between the cytotoxicity of bortezomib and the expression level of the proteasome 20S core particle subunit β5 (PSMB5). Intriguingly, we identified PSMB5 as a direct target of miR-383. Increased expression of miR-383 resulted in decreased PSMB5 expression and increased sensitivity to bortezomib in OS cells.

Conclusions

In summary, our findings present the initial comprehensive analysis of the function of miR-383 in OS. The outcomes indicate that miR-383 may augment the anticancer effect of bortezomib through PSMB5 repression, offering a novel therapeutic approach in OS and a fresh pathway for proteasome regulation.

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Data availability

Data can be accessed with a reasonable request to the corresponding author.

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Funding

This work was supported by grants from the key research and development plan of Shaanxi Province (2023-YBSF-290).

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Authors and Affiliations

  1. Department of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, Shaanxi, China

    Haifan Wang, Chuanyi Bai, Xiaoqian Dang & Haoyu Wang

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  1. Haifan Wang
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  2. Chuanyi Bai
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  3. Xiaoqian Dang
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  4. Haoyu Wang
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Contributions

HW wrote the main manuscript text; CB gave funding support; XD provided the technical support; HW concept of the ideal and supervised the whole study. All authors reviewed the manuscript.

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Correspondence to Haoyu Wang.

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Wang, H., Bai, C., Dang, X. et al. MiR-383 sensitizes osteosarcoma cells to bortezomib treatment via down-regulating PSMB5. Mol Biol Rep 51, 170 (2024). https://doi.org/10.1007/s11033-023-08964-7

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