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MiR-34c-5p Inhibition Affects Bax/Bcl2 Expression and Reverses Bortezomib Resistance in Multiple Myeloma Cells

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Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

Developing resistance to anticancer drugs complicates the clinical treatment of multiple myeloma patients. Previous studies revealed a link between the unfolded protein response (UPR) and miRNAs with acquired drug resistance. This study aimed to determine the expression profile of XBP1, hsa-miR-34c-5p, hsa-miR-214, and hsa-miR-30c-2* in resistant and sensitive multiple myeloma cell lines to a proteasome inhibitor, bortezomib. After establishing bortezomib-resistant cells, the expression level of XBP1, hsa-miR-214, hsa-miR-34c-5p, and hsa-miR-30c-2* in both cell lines were assessed by qRT-PCR. Hsa-miR-34c-5p was suppressed to study its effect on the expression profile of Bax/Bcl-2. Statistical analysis was done by t-test in two clinically resistant and sensitive cells to bortezomib. MTT assay confirmed the creation of the resistant cell line. The qRT-PCR screening showed a significant difference between XBP1 and miR-34c-5p levels in resistant and sensitive cells. Following hsa-miR-34c-5p blockage, while Bax was overexpressed, Bcl-2 expression was reduced in the resistant cell line, overcoming cells resistant to bortezomib. Our findings demonstrate miR-34c-5p is differentially expressed between bortezomib-sensitive and -resistant MM cells. Inhibiting miR-34c-5p re-sensitized resistant cells to bortezomib by modulating Bax/Bcl-2 expression, suggesting this miRNA regulates apoptosis and drug resistance and may be a promising therapeutic target for overcoming proteasome inhibitor resistance in MM.

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Funding

This research was supported by Ahvaz Jundishapur University of Medical Sciences Grant No. CMRC-9903.

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Authors and Affiliations

  1. Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jondishapur University of Medical Sciences, Ahvaz, Iran

    Emad Matour, Zari Tahannejad Asadi & Behrouz Taheri

  2. Department of Laboratory Sciences, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Emad Matour & Zari Tahannejad Asadi

  3. Department of Internal Medicine, School of Medicine, Firoogar General Hospital, Iran University of Medical Science, Tehran, Iran

    Ahmad Ahmadzadeh Deilami

  4. Department of Anatomical Sciences, Cellular & Molecular Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Seyed Saeed Azandeh & Behrouz Taheri

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  1. Emad Matour
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  2. Zari Tahannejad Asadi
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Correspondence to Behrouz Taheri.

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This study was approved by the ethics committee of Ahvaz Jundishapur University of Medical Sciences (Ethical code: IR.AJUMS.REC.1399.178).

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Matour, E., Asadi, Z.T., Deilami, A.A. et al. MiR-34c-5p Inhibition Affects Bax/Bcl2 Expression and Reverses Bortezomib Resistance in Multiple Myeloma Cells. Indian J Hematol Blood Transfus (2024). https://doi.org/10.1007/s12288-024-01742-w

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