多发性骨髓瘤癌症干细胞（MMSC）被认为是多发性骨髓瘤（MM）耐药和最终复发的主要原因，microRNA（miRNA）共同参与MM的进展。然而，miR-138在MMSC中的发病机制仍不完全清楚。本研究的目的是探讨miR-138在多发性骨髓瘤中的机制和作用。收集患者和正常对照的骨髓样本和外周血。使用基于磁性的癌症干细胞分离试剂盒分离和提取 MMSC。进行实时定量PCR（RT-qPCR）以确定mRNA水平。应用Western blot检测蛋白质水平。采用MTT和流式细胞仪检测MMSC的增殖和凋亡情况。最后，进行双荧光素酶报告基因检测，证实配对盒5（PAX5）是miR-138的直接靶标。与正常组相比，患者体内miR-138的表达显着上调，且表达量显着上调。 miR-138的表达与PAX5呈负相关。此外，下调miR-138在体外和体内促进细胞凋亡并抑制MMSC的增殖。下调 miR-138 调节 PAX5、Bcl-2、Bax 和 Caspase-3 的表达。 PAX5是miR-138的直接靶标。综上所述，miR-138在MM中具有致癌作用，并且miR-138通过靶向PAX5来调节MMSC的增殖和凋亡。 miR-138有可能成为治疗MM的新药物靶点。版权所有©2024 Elsevier B.V.保留所有权利。

Multiple myeloma cancer stem cells (MMSC) have been considered as the leading cause of multiple myeloma (MM) drug resistance and eventual relapse, microRNAs (miRNAs) collectively participate in the progression of MM. However, the pathogenesis of miR-138 in MMSC is still not fully understood.The intention of this study was to investigate the mechanism and role of miR-138 in multiple myeloma.Bone marrow samples and peripheral blood from patients and normal controls were collected. Use Magnet-based Cancer Stem Cell Isolation Kit to separate and extract MMSC. Real-time quantitative PCR (RT-qPCR) was carried out to determine mRNA level. Western blot was applied to detect protein levels. MTT and flow cytometry were conducted to examine the proliferation and apoptosis of MMSC. Finally, dual-luciferase reporter gene assays were performed to confirm that paired box 5 (PAX5) is a direct target for miR-138.Compared with normal group, the expression of miR-138 in patients was significantly up-regulated, and the expression of miR-138 was in a negative correlation with PAX5. Additionally, downregulated miR-138 facilitated the apoptosis and inhibited the proliferation of MMSC in vitro and in vivo. Downregulated miR-138 moderated the expression of PAX5, Bcl-2, Bax, and Caspase-3. PAX5 was a direct target of miR-138.Taken together, miR-138 plays a carcinogenic role in MM, and miR-138 adjusted the proliferation and apoptosis of MMSC by targeting PAX5. miR-138 has the probability of becoming a new medicinal target for the treatment of MM.Copyright © 2024 Elsevier B.V. All rights reserved.