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

Zhao, Wei; Qin, Pan; Zhang, Da; Cui, Xichun; Gao, Jing; Yu, Zhenzhu; Chai, Yuting; Wang, Jiaxiang; Li, Juan

doi:10.18632/aging.102406

Cited by 115Extracellular vesicles in diseaseCancer-related molecular mechanisms researchCircular RNAs in diseases

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

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Zhao, Wei, Qin, Pan, Zhang, Da, Cui, Xichun, Gao, Jing, Yu, Zhenzhu, Chai, Yuting, Wang, Jiaxiang +1 more·2019·Aging

DOI 10.18632/aging.102406PMC PMC6874467

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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.

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Co-cultures of BM-MSC-derived exosomes with Saos-2, MG-63, and MNNG/HOS OS cell lines led to increased expression of PVT1, a long noncoding RNA that contributes to OS growth and metastasis.
“In another study, co-cultures of BM-MSC-derived exosomes with Saos-2, MG-63, and MNNG/HOS OS cells lines led to the increased expression of PVT1, a long, noncoding RNA that contributes to OS growth and metastasis [121].”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [121]

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Authors: Zhao, W., Qin, P., Zhang, D., Cui, X., Gao, J., Yu, Z., Chai, Y., Wang, J., & Li, J.
Affiliations: First Affiliated Hospital of Zhengzhou University (CN)
Corresponding author: Li, Juan
ORCID: Zhao, Wei
Zhang, Da
Gao, Jing
Wang, Jiaxiang
Li, Juan
Venue: Aging
Publisher: Impact Journals, LLC
Published: 2019-11-07
Volume: 11
Issue: 21
Pages: 9581-9596
ISSN: 1945-4589 (ISSN-L)
DOI: 10.18632/aging.102406
PMC: PMC6874467
OpenAlex: W2984884798
Cited by: 115
References: 42
Citations by year: 2026: 5 · 2025: 14 · 2024: 18 · 2023: 16 · 2022: 26 · 2021: 19 · 2020: 17
FWCI: 5.13
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: cc-by
Locations: Aging (publishedVersion)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
Keywords: bone marrow mesenchymal stem cells, exosomes, osteosarcoma, ERG, miR-183-5p, tumor growth, metastasis, protein stabilization, ubiquitination, tumor microenvironment, cell proliferation, cell migration
MeSH terms: Transcriptional Regulator ERG, Animals, Bone Neoplasms, Humans, Mice, Inbred BALB C, Mice, Nude, Neoplasm Metastasis, Neoplasm Transplantation, Osteosarcoma, MicroRNAs, Cell Line, Tumor, Exosomes, Primary Cell Culture, RNA, Long Noncoding

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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

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