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MicroRNA-29b-3p reduces cisplatin resistance in non-small cell lung cancer by targeting myeloid cell leukemia-1

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Abstract

Introduction

Non-small cell lung cancer (NSCLC) is a heterogeneous series of tumors. Given the implication of microRNA-29b-3p (miR-29b-3p) in cisplatin resistance in NSCLC, this study expounded on the further mechanism.

Methods

A549 cells and cisplatin-resistant cells A549/DDP were selected. A549/DDP cells were manipulated with miR-29b-3p mimics/MCL-1 siRNA. miR-29b-3p and MCL levels were assessed. Cell sensitivity to cisplatin of different concentrations was examined by CCK-8. A549/DDP cell apoptosis under 10 µM cisplatin treatment was tested by flow cytometry. The targeted relationship between miR-29b-3p and MCL-1 was analyzed by TargetScan database and dual-luciferase assay. miR-29b-3p and MCL-1 were overexpressed to study whether miR-29b-3p regulated A549/DDP cell drug resistance by targeting MCL-1. To verify the effect of miR-29b-3p on DDP sensitivity in vivo, nude mice were subcutaneously injected with A549/DDP cells carrying the miR-29b-3p overexpressing lentiviral vector or the corresponding control vector to establish the nude mouse xenograft tumor model, and after 3 weeks, injected with DDP via tail vein for 2 weeks.

Results

miR-29b-3p level in A549/DDP cells was diminished and MCL-1 expression was raised. miR-29b-3p overexpression or MCL-1 silencing enhanced A549/DDP cell sensitivity to cisplatin by promoting apoptosis. miR-29b-3p targeted MCL-1. MCL-1 overexpression partially averted miR-29b-3p overexpression-promoted cisplatin sensitivity and apoptosis. Tumor volume/weight/MCL-1 level in the A549/DDP/miR mimics + DDP group were reduced, and miR-29b-3p was up-regulated versus the A549/DDP/mimics NC + DDP group. Overexpression of miR-29b-3p induced apoptosis in tumor tissues of NSCLC mice.

Conclusion

miR-29b-3p targeted MCL-1, thus promoting apoptosis and enhancing A549/DDP cell sensitivity to cisplatin.

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Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

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Funding

This research was supported by grants from “Key research and Development Program of Anhui Province in 2021 (202104j07020055)”; “Beijing Science and Technology Innovation Medical Development Foundation (KC2021-JX-0186–46)”and “Guiding project of Suzhou Science and Technology Development Plan (SKJYD2021014)”.

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Author notes

  1. Yuanjun Cheng and Bin Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiothoracic Surgery, People’s Hospital of Chizhou, No. 3 Baiya Road, Guichi District, Chizhou, 247000, China

    Yuanjun Cheng, Bin Chen, Xuxiao Dong & Jie Yao

  2. Department of Cardiothoracic Surgery, The First People’s Hospital of Taicang, Taicang, 215400, Suzhou, China

    Jian Shu

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  1. Yuanjun Cheng
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  2. Bin Chen
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Contributions

YJC and BC are the guarantor of integrity of the entire study and contributed to the study design; XXD contributed to the literature research, data acquisition; JS contributed to the study concepts, statistical analysis; YJC contributed to the definition of intellectual content; JY contributed to the data analysis, manuscript editing; All authors read and approved the final manuscript.

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Correspondence to Jian Shu or Jie Yao.

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All authors declare that there is no conflict of interests in this study.

Ethical approval

All animal experiments in this study were approved by the Animal Ethics Committee of our hospital. All the efforts were made to minimize the pain of the mice (approved number: 2021-KY-011).

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Cheng, Y., Chen, B., Dong, X. et al. MicroRNA-29b-3p reduces cisplatin resistance in non-small cell lung cancer by targeting myeloid cell leukemia-1. Mol. Cell. Toxicol. (2024). https://doi.org/10.1007/s13273-024-00438-6

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