Human bone marrow-derived mesenchymal stem overexpressing microRNA-124-3p inhibit DLBCL progression by downregulating the NFATc1/cMYC pathway

• Published in: Stem cell research & therapy Vol. 14; no. 1; p. 148
• Main Authors: Zhao, Xiaoxuan, Xu, Mingxi, Hu, Xuemeng, Ding, Xiaolei, Zhang, Xian, Xu, Liye, Li, Li, Sun, Xiuhua, Song, Jincheng
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 29-05-2023; BioMed Central; BMC
• Subjects: Apoptosis; B cells; B-cell lymphoma; Bone marrow; Bone Marrow - metabolism; Cancer; Cell growth; Cell proliferation; Coculture Techniques; Development and progression; DLBCL; Down-Regulation; Exosomes; Exosomes - genetics; Exosomes - metabolism; Genes; Human bone marrow mesenchymal stem cells; Humans; Laboratories; Lymphoma; Lymphoma, Large B-Cell, Diffuse - metabolism; Mesenchymal stem cells; MicroRNA; MicroRNA-124-3p; MicroRNAs; MicroRNAs - metabolism; miRNA; NFATC Transcription Factors - genetics; NFATC Transcription Factors - metabolism; NFATc1; Non-Hodgkin's lymphomas; Plasmids; Proteins; Stem cells; Tumors; Japan; China; St Louis Missouri; United Kingdom > UK; United States > US; MicroRNA-124-3p; DLBCL; NFATc1; Human bone marrow mesenchymal stem cells; Exosomes
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-023-03373-w

Exosomes play important roles in intercellular communication by delivering microRNAs (miRNAs) that mediate tumor initiation and development, including those in diffuse large B cell lymphoma (DLBCL). To date, however, limited studies on the inhibitory effect of exosomes derived from human bone marrow mesenchymal stem cells (hBMSCs) on DLBCL progression have been reported. Therefore, this study aimed to investigate the role of hBMSC exosomes carrying microRNA-124-3p in the development of DLBCL.
Microarray-based expression analysis was adopted to identify differentially expressed genes and regulatory miRNAs, which revealed the candidate NFATc1. Next, the binding affinity between miR-124-3p and NFATc1 was detected by luciferase activity assays. The mechanism underlying NFATc1 regulation was investigated using lentiviral transfections. Subsequently, DLBCL cells were cocultured with exosomes derived from hBMSCs transfected with a miR-124-3p mimic or control. Proliferation and apoptosis were measured in vitro. Finally, the effects of hBMSC-miR-124-3p on tumor growth were investigated in vivo.
MiR-124-3p was expressed at low levels, while NFATc1 was highly expressed in DLBCL cells. MiR-124-3p specifically targeted and negatively regulated the expression of NFATc1 in DLBCL cells, upregulated miR-124-3p-inhibited DLBCL cell proliferation and promoted apoptosis. The miR-124-3p derived from hBMSCs inhibits tumor growth both in vivo and in vitro via downregulation of the NFATc1/cMYC pathway.
Human bone marrow-derived mesenchymal stem cell overexpressing microRNA-124-3p represses the development of DLBCL through the downregulation of NFATc1.