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

抑制细胞外囊泡 miR-10a 分泌诱导多发性骨髓瘤骨髓基质细胞凋亡

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作者:Tomohiro Umezu, Satoshi Imanishi, Seiichiro Yoshizawa, Chiaki Kawana, Junko H Ohyashiki, Kazuma Ohyashiki

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.

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