Human Bone Marrow-Derived Mesenchymal Stem Cell-Secreted Exosomes Overexpressing Microrna-124-3p Inhibit DLBCL Progression By Downregulating  NFATc1

Abstract

Background: 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-derived mesenchymal stem cells (hBMSCs) on DLBCL progression have been reported. Therefore, this study aimed to investigate the role of hBMSC-secreted exosomes carrying microRNA-124-3p in the development of DLBCL.Methods: 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 using 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-derived miR-124-3p on tumor growth were investigated in vivo.Results: MiR-124-3p was downregulated while NFATc1 was upregulated 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. In addition, we found that hBMSC-derived exosomes carrying miR-124-3p repressed DLBCL cell proliferation both in vitro and in vivo.Conclusion: hBMSC-derived exosomal miR-124-3p represses the development of DLBCL through the downregulation of NFATc1.

Emerging Concepts on the Role of Extracellular Vesicles and Its Cargo Contents in Glioblastoma-Microglial Crosstalk

“…Brain endothelium cell derived (bEND.3) exosomes loaded with paclitaxel and DOX crossed the BBB and significantly reduced the GBM tumor growth which was evident by the decreased fluorescent intensity in xenotransplanted zebrafish cancer model [181][182][183][184]. Various studies [185][186][187] on human bone marrow-derived exosome (hBMSC)-containing miRNA and lncRNA have reported decrease in glioma cell proliferation, invasion, and enhanced chemosensitivity to temozolomide (TMZ). As EVs carry immunomodulatory molecules, in vivo studies confirmed that exosomes from DCs loaded with chaperone rich cell-lysates elicits a potential T cell immune response against intracranial glioma in mice [188].…”