Bone marrow‐derived mesenchymal stem cell‐derived exosomal microRNA‐208a promotes osteosarcoma cell proliferation, migration, and invasion

Abstract

A recent study has discovered that mesenchymal stem cells (MSCs) are recruited into tumors and MSC-derived exosomes in a novel mechanism of cell-to-cell communication in human cancers. Here, in this study, we explore the impact of the microRNA-208a (miR-208a)-enriched exosomes derived from bone marrow-derived mesench- ymal stem cells (BMSCs) on osteosarcoma cells. Human osteosarcoma cells MG-63and Saos-2 were exposed to BMSCs-derived exosomes treated with either miR-208a mimic or inhibitor. The MTT assay, transwell migration assay, and soft agar colony formation assay were used to evaluate the viability, migration, and clonogenicity of osteosarcoma cells. Bioinformatics analysis and dual-luciferase reporter gene assays validated the targeted relationship between miR-208a and PDCD4. Western blot assay was used to detect the expression of PDCD4 and related proteins in the ERK1/2 pathway in osteosarcoma cells. BMSCs communicated with osteosarcoma cells via exosomes. Ectopic expression of miR-208a was shown to increase the viability, migration, and clonogenicity of osteosarcoma cells. Analysis of the exosomal content identified miR-208a as a mediator of the exosomal effects on osteosarcoma cells in part via downregulation of PDCD4 and activating the ERK1/2 pathway. In summary, our study illuminates that BMSC-derived exosomal miR-208a enhances the progression of osteosarcoma. K E Y W O R D Sbone marrow-derived mesenchymal stem cells, exosome, microRNA-208a, osteosarcoma, PDCD4

Exosomal PD-L1 Derived From Osteosarcoma is Associated With Pulmonary Metastasis for Patients With Osteosarcoma

“…However, the complexity of Srexosomes isolated from OS patients cann't explain the effect of osteosarcoma derived exosomes on the tumor pathogenesis. Qin et al MSC-derived exosomal miRNA as a mediator of the exosomal effects on osteosarcoma enhanced the progression of osteosarcoma [3]. Based on above mentioned reason, we isolated exosomes from 143B cells and interacted with osteosarcoma cells in vitro.…”

“…Inward budding of late endosomes develop into intracellular multivesicular endosomes and RNA, DNA, proteins and other small moleculars are encapsulated into exosomes during the formation of exosome [1,2]. Various types of cells such as immune cells, broblast and endothelial cells, release exosomes into the extracellular space and microenviroment, involving the tumor pathogenesis [3,4]. Recent studies reported that tumor cell-derived exosomes stimulated cancer and sarcoma cell growth, survival, metastasis, angiogenesis and chemotherapy resistance [5][6][7][8][9][10][11].…”

Extracellular vesicles produced by bone marrow mesenchymal stem cells attenuate renal fibrosis, in part by inhibiting the RhoA/ROCK pathway, in a UUO rat model

“…In addition, BMSC infusion has been reported to improve recovery from the acute kidney injury (AKI) induced by ischemia/reperfusion [10]. However, BMSCs can also be tumorigenic and are often inappropriately retained by target tissues, limiting their clinical usefulness [9]. Emerging data suggest that BMSCs may promote regeneration in a paracrine/endocrine manner by delivering EVs to specific tissues [8].…”

“…BMSCs are generally recognized for their ability to self-renew and differentiate into multiple lineages; however, this can lead to teratoma formation by transplanted BMSCs, which limits their therapeutic effectiveness [8]. Recently it has become increasingly clear that BMSC-derived extracellular vesicles (BMSC-EVs) have important biological functions and molecular mechanisms [9], and may serve as an alternative to therapies based on BMSC transplantation [8]. EVs, which originate from BMSC endosomal compartments, can modulate inflammation [10][11][12].…”

miRNA-6087 Delivered by Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells, Inhibition of miR-6087 in Exosomes can Significantly Inhibit the Proliferation, Invasion and Migration of Tumor Cells.

“…In previous studies, many studies focused on the relationship between miRNA and OS malignant phenotype, and revealed some effects of miRNA on OS cell growth.Fa Qin et al reported that Bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-208a promotes osteosarcoma cell proliferation, migration, and invasion [47].As a member of miRNAs involved in tumor progression, miRNA-6087 plays an important role in the progression of bladder cancer and liver cancer. We use miRNA-6087 to enrich exosomes in large quantities, and nd that miRNA-6087 is down-regulated in exosomes.…”