MicroRNA-138 promotes the progression of multiple myeloma through targeting paired PAX5

Abstract

BackgroundMultiple 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. ObjectiveThe intention of this study was to investigate the mechanism and role of miR-138 in multiple myeloma. MethodBone 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. ResultsCompared 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. ConclusionTaken 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.