Long non-coding RNA PVT1 encapsulated in bone marrow mesenchymal stem cell-derived exosomes promotes osteosarcoma growth and metastasis by stabilizing ERG and sponging miR-183-5p

Abstract

Exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) promote osteosarcoma cell proliferation and migration, while the underlying mechanism remains unknown. Since the long non-coding RNA PVT1 has been reported to be upregulated in osteosarcoma cells and contributes to its growth and metastasis, we aim to investigate whether BMSC-derived exosomes promote osteosarcoma growth and metastasis via transporting PVT1 into osteosarcoma cells. The PVT1 expression in BMSC-derived exosomes was markedly higher than that in osteosarcoma cell-derived exosomes. The co-culturing of BMSC-derived exosomes and osteosarcoma cells (Saos-2, MG-63, and MNNG/HOS cell lines) significantly raised PVT1 expression of osteosarcoma cells. The direct binding between PVT1 and the oncogenic protein ERG was confirmed using RNA immunoprecipitation and RNA pull-down assays, and the transported PVT1 promotes osteosarcoma cell proliferation and migration via inhibiting degradation and ubiquitination of ERG. PVT1 also increased ERG expression through sponging miR-183-5p. In summary, our findings indicated that BMSC-derived exosomes encapsulate PVTl and transport it into osteosarcoma cells, and the transported PVT1 promotes tumor growth and metastasis by inhibiting ubiquitination and promoting expression of ERG in osteosarcoma cells. These data provide a novel insight into the mechanism of BMSC-derived exosomes in affecting osteosarcoma progression.