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MicroRNA-424-5p enhances chemosensitivity of breast cancer cells to Taxol and regulates cell cycle, apoptosis, and proliferation

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Abstract

Combination therapy has been considered as a potential method to overcome the BC chemoresistance. MicroRNAs (miRs) have been suggested as a therapeutic factor in the combination therapy of BC. This project aimed at examining the possible activity and molecular function of miR-424-5p and Taxol combination in the human BC cell line. MDA-MB-231 cells were treated with miR-424-5p mimics and Taxol, in a combined manner or separately. We used the MTT test for assessing the cell proliferation. In addition, flow-cytometry was used for evaluating apoptosis and cell-cycle. Expression levels of underlying molecular factors of miR-424-5p were assessed using western-blotting and qRT-PCR. The obtained results demonstrated that miR-424-5p repressed BC cell proliferation and sensitized these cells to Taxol treatment through the induction of apoptosis. Further investigations showed that miR-424-5p might increase BC chemosensitivity through the regulation of apoptosis-related factors including P53, Caspase-3, Bcl-2, and Bax as well as the proliferation-related gene c-Myc. Moreover, miR-424-5p restoration in combination with Taxol treatment decreased the colony formation by regulating Oct-4 and led to G2 arrest via modulating Cdk-2 expression. Western-blotting demonstrated that miR-424-5p may perform its anti-chemoresistance role by regulating the PD-L1 expression and controlling PTEN/PI3K/AKT/mTOR. Overall, the upregulation of miR-424-5p was indicated to upregulate the sensitivity of BC cells to treatment with Taxol. MiR-424-5p might regulate the chemosensitivity of the BC cell line by modulating PD-L1 and controlling the PTEN/mTOR axis. Therefore, the combination of miR-424-5p with Taxol would represent a novel procedure to treat against BC.

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Acknowledgements

This study was considered as a part of the project entitled “The evaluation of non coding RNAs role in human cancers” which is conducted at University of Tabriz. We would like to thank Tabriz Immunology Research Center, Iran for providing facilities to carry out this project.

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No funding was received.

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Authors and Affiliations

  1. Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

    Narges Dastmalchi, Reza Safaralizadeh, Mohammad Ali Hosseinpourfeizi & Seyed Mahdi Banan Khojasteh

  2. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Behzad Baradaran

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  1. Narges Dastmalchi
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  2. Reza Safaralizadeh
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  3. Mohammad Ali Hosseinpourfeizi
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Correspondence to Reza Safaralizadeh.

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Dastmalchi, N., Safaralizadeh, R., Hosseinpourfeizi, M.A. et al. MicroRNA-424-5p enhances chemosensitivity of breast cancer cells to Taxol and regulates cell cycle, apoptosis, and proliferation. Mol Biol Rep 48, 1345–1357 (2021). https://doi.org/10.1007/s11033-021-06193-4

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  • DOI: https://doi.org/10.1007/s11033-021-06193-4

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