Zeliha EMRENCE, Şeyma PUNAR, Merve KESKİN, Berra SÜMER, Büşra KARAÇAM, Neslihan ABACI, Sema Sırma EKMEKCİ
Kocaeli Üniversitesi Sağlık Bilimleri Dergisi - 2026;12(3):244-249
Objective: Bortezomib is a key proteasome inhibitor used in multiple myeloma treatment; however, acquired resistance limits its long-term clinical efficacy. MicroRNAs are important post-transcriptional regulators involved in apoptosis, stress response, cellular adaptation, and drug resistance. This study aimed to investigate the expression profiles of selected microRNAs potentially associated with bortezomib resistance in multiple myeloma cell models. Methods: Bortezomib-resistant U266 and RPMI-8226 multiple myeloma cells were generated by continuous exposure to gradually increasing concentrations of bortezomib. The expression levels of miR-25, miR-30c, miR-34a, miR-34c, miR-200b, miR-200c, miR-326, miR-429, miR-449a, miR-449b, miR-499a, miR-582, and miR-708 were analyzed in resistant and control cells using quantitative real-time PCR. U6 snRNA was used as the endogenous control, and relative expression levels were calculated using the 2?DeltaDeltaCt method. Results: Bortezomib-resistant U266 and RPMI-8226 cells exhibited both shared and cell line-specific miRNA expression changes. miR-34a, miR-34c, miR-326, miR-429, miR-449a, and miR-449b were significantly upregulated in both resistant cell lines. miR-25, miR-200c, and miR-708 were increased only in resistant RPMI-8226 cells. In contrast, miR-200b, miR-499a, and miR-582 showed opposite expression patterns between the two resistant models, while miR-30c expression remained unchanged. Conclusion: Acquired bortezomib resistance in multiple myeloma was associated with both common and cell line-specific miRNA alterations. The consistent upregulation of miR-34, miR-326, and miR-449 family members suggests their involvement in adaptive responses to proteasome inhibition, whereas divergent expression patterns of other miRNAs indicate heterogeneous resistance mechanisms. Further studies are needed to clarify the functional roles of these miRNAs in bortezomib resistance.
