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.

抗癌药物产生耐药性使多发性骨髓瘤患者的临床治疗变得复杂。先前的研究揭示了未折叠蛋白反应（UPR）与具有获得性耐药性的 miRNA 之间的联系。本研究旨在确定 XBP1、hsa-miR-34c-5p、hsa-miR-214 和 hsa-miR-30c-2* 在对蛋白酶体抑制剂硼替佐米耐药和敏感的多发性骨髓瘤细胞系中的表达谱。建立硼替佐米耐药细胞后，通过 qRT-PCR 评估两种细胞系中 XBP1、hsa-miR-214、hsa-miR-34c-5p 和 hsa-miR-30c-2* 的表达水平。抑制 Hsa-miR-34c-5p 以研究其对 Bax/Bcl-2 表达谱的影响。通过对两种临床上对硼替佐米耐药和敏感的细胞进行 t 检验进行统计分析。 MTT 测定证实了耐药细胞系的产生。 qRT-PCR 筛选显示耐药细胞和敏感细胞中 XBP1 和 miR-34c-5p 水平存在显着差异。 hsa-miR-34c-5p 阻断后，虽然 Bax 过表达，但耐药细胞系中的 Bcl-2 表达降低，克服了细胞对硼替佐米的耐药性。我们的研究结果表明，miR-34c-5p 在硼替佐米敏感和耐药的 MM 细胞中表达存在差异。抑制 miR-34c-5p 通过调节 Bax/Bcl-2 表达使耐药细胞对硼替佐米重新敏感，表明该 miRNA 调节细胞凋亡和耐药性，可能是克服 MM 中蛋白酶体抑制剂耐药性的有希望的治疗靶点。