Dataset Information

Induction of multiple myeloma bone marrow stromal cell apoptosis by inhibiting extracellular vesicle miR-10a secretion.

ABSTRACT: Bone marrow stromal cells (BMSCs) interact with multiple myeloma (MM) cells in the bone marrow and create a permissive microenvironment for MM cell proliferation and survival. In this study, we investigated the role of extracellular vesicles (EVs) from BMSCs derived from patients with MM (MM-BMSCs). EV-encapsulated miR-10a expression was high while intracellular miR-10a was low in MM-BMSCs. We therefore hypothesized that miR-10a was packaged into EVs that were actively released into the extracellular space. Inhibition of EV release resulted in accumulation of intracellular miR-10a, inhibition of cell proliferation, and induction of apoptosis in MM-BMSCs. In contrast, proliferation and apoptosis of BMSCs derived from healthy individuals were unaffected by inhibition of EV release. Furthermore, miR-10a derived from MM-BMSCs was transferred into MM cells via EVs and enhanced their proliferation. These results suggest that inhibition of EV release induced apoptosis in MM-BMSCs and inhibited MM cell proliferation, indicating a possible role for MM-BMSC-targeted therapy.

SUBMITTER: Umezu T

PROVIDER: S-EPMC6855114 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Induction of multiple myeloma bone marrow stromal cell apoptosis by inhibiting extracellular vesicle miR-10a secretion.

Umezu Tomohiro T Imanishi Satoshi S Yoshizawa Seiichiro S Kawana Chiaki C Ohyashiki Junko H JH Ohyashiki Kazuma K

Blood advances 20191101 21

Bone marrow stromal cells (BMSCs) interact with multiple myeloma (MM) cells in the bone marrow and create a permissive microenvironment for MM cell proliferation and survival. In this study, we investigated the role of extracellular vesicles (EVs) from BMSCs derived from patients with MM (MM-BMSCs). EV-encapsulated miR-10a expression was high while intracellular miR-10a was low in MM-BMSCs. We therefore hypothesized that miR-10a was packaged into EVs that were actively released into the extracel ...[more]

PMID: 31698453

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Project description:AbstractInteraction with bone marrow stromal cells (BMSCs) has been suggested as an important mechanism for the progression of multiple myeloma (MM) cells, while exosomes are crucial mediators for cell-to-cell communication. The study was to investigate the miRNA profile changes in exosomes released by BMSCs of MM patients and explore their possible function roles.The microarray datasets of exosomal miRNAs in BMSCs were downloaded from the Gene Expression Omnibus database (GSE110271: 6 MM patients, 2 healthy donors; GSE78865: 4 donors and 2 MM patients; GSE39571: 7 MM patients and 4 controls). The differentially expressed miRNAs (DEMs) were identified using the LIMMA method. The target genes of DEMs were predicted by the miRwalk 2.0 database and the hub genes were screened by constructing the protein-protein interaction (PPI) network, module analysis and overlapping with the differentially expressed genes (DEGs) after overexpression or knockout of miRNAs.Three downregulated DEMs were found to distinguish MM from normal and MM-MGUS controls in the GSE39571 dataset; one downregulated and one upregulated DEMs (hsa-miR-10a) could differentiate MM from normal and MM-MGUS controls in the GSE110271-GSE78865 merged dataset. Furthermore, 11 downregulated (hsa-miR-16) and 1 upregulated DEMs were shared between GSE39571 and merged dataset when comparing MM with normal samples. The target genes were predicted for these 17 DEMs. PPI with module analysis showed IGF1R and CCND1 were hub genes and regulated by hsa-miR-16. Furthermore, EPHA8 was identified as a DEG that was downregulated in MM cells when the use of has-miR-10a mimics; while IGF1R, CCND1, CUL3, and ELAVL1 were also screened as DEGs that were upregulated in MM cells when silencing of hsa-miR-16.BMSCs-derived exosomal miR-10a and miR-16 may be involved in MM progression by regulating EPHA8 or IGF1R/CCND1/CUL3/ELAVL1, respectively. These exosomal miRNAs or genes may represent potential biomarkers for diagnosis of MM and prediction of progression and targets for developing therapeutic drugs.

Dataset Information

Induction of multiple myeloma bone marrow stromal cell apoptosis by inhibiting extracellular vesicle miR-10a secretion.

Publications

Induction of multiple myeloma bone marrow stromal cell apoptosis by inhibiting extracellular vesicle miR-10a secretion.

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