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Indian Journal of Hematology and Blood Transfusion

11.04.2024 | ORIGINAL ARTICLE

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

verfasst von: Emad Matour, Zari Tahannejad Asadi, Ahmad Ahmadzadeh Deilami, Seyed Saeed Azandeh, Behrouz Taheri

Erschienen in: Indian Journal of Hematology and Blood Transfusion

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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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Titel: MiR-34c-5p Inhibition Affects Bax/Bcl2 Expression and Reverses Bortezomib Resistance in Multiple Myeloma Cells
verfasst von: Emad Matour
Zari Tahannejad Asadi
Ahmad Ahmadzadeh Deilami
Seyed Saeed Azandeh
Behrouz Taheri
Publikationsdatum: 11.04.2024
Verlag: Springer India
Erschienen in: Indian Journal of Hematology and Blood Transfusion
Print ISSN: 0971-4502
Elektronische ISSN: 0974-0449
DOI: https://doi.org/10.1007/s12288-024-01742-w

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

Abstract

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