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

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2024-07-01 DOI:10.1016/j.mrfmmm.2024.111869

Xiao Yan , Keting Wang , Cong Shi , Kaihong Xu , Binbin Lai , Shujun Yang , Lixia Sheng , Ping Zhang , Ying Chen , Qitian Mu , Guifang Ouyang

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引用次数: 0

Abstract

Background

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.

Objective

The intention of this study was to investigate the mechanism and role of miR-138 in multiple myeloma.

Method

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.

Results

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.

Conclusion

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.

查看原文本刊更多论文

MicroRNA-138 通过靶向配对的 PAX5 促进多发性骨髓瘤的进展。

背景：多发性骨髓瘤癌干细胞（MMSC）被认为是多发性骨髓瘤（MM）耐药和最终复发的主要原因，微RNA（miRNA）共同参与了MM的进展。然而，miR-138在MMSC中的发病机制仍未完全明了：本研究旨在探讨 miR-138 在多发性骨髓瘤中的作用机制：方法：收集患者和正常对照组的骨髓和外周血样本。使用磁性癌症干细胞分离试剂盒分离并提取 MMSC。采用实时定量 PCR（RT-qPCR）检测 mRNA 水平。采用 Western 印迹检测蛋白质水平。采用 MTT 和流式细胞术检测 MMSC 的增殖和凋亡。最后，通过双荧光素酶报告基因实验证实配对框 5（PAX5）是 miR-138 的直接靶标：结果：与正常组相比，患者体内 miR-138 的表达明显上调，且 miR-138 的表达与 PAX5 呈负相关。此外，下调的 miR-138 可促进 MMSC 的体外和体内凋亡并抑制其增殖。下调的 miR-138 可调节 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中起致癌作用，miR-138通过靶向PAX5调节MMSC的增殖和凋亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 生物-毒理学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

51 days

期刊介绍： Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.