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Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2

Bone marrow-derived mesenchymal stem cell (BMSC) is one crucial component of the multiple myeloma (MM) microenvironment and supports the malignant progression of MM. Whether BMSCs act on MM cells via exosomes has not been well characterized. Herein, we used microarrays to screen out differentially e...

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Autores principales: Gu, Jianmei, Wang, Maoye, Wang, Xinfeng, Li, Jiao, Liu, Haiyan, Lin, Zenghua, Yang, Xi, Zhang, Xu, Liu, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921260/
https://www.ncbi.nlm.nih.gov/pubmed/35300408
http://dx.doi.org/10.3389/fcell.2022.862524
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author Gu, Jianmei
Wang, Maoye
Wang, Xinfeng
Li, Jiao
Liu, Haiyan
Lin, Zenghua
Yang, Xi
Zhang, Xu
Liu, Hong
author_facet Gu, Jianmei
Wang, Maoye
Wang, Xinfeng
Li, Jiao
Liu, Haiyan
Lin, Zenghua
Yang, Xi
Zhang, Xu
Liu, Hong
author_sort Gu, Jianmei
collection PubMed
description Bone marrow-derived mesenchymal stem cell (BMSC) is one crucial component of the multiple myeloma (MM) microenvironment and supports the malignant progression of MM. Whether BMSCs act on MM cells via exosomes has not been well characterized. Herein, we used microarrays to screen out differentially expressed miRNAs in BMSCs from patients with MM (MM-MSCs) or benign diseases (BD-MSCs). We found that miR-483-5p was highly expressed in MM-MSCs, which may be transported through exosomes from MM-MSCs to MM cells to increase miR-483-5p expression in them. We then investigated the role and mechanism of miR-483-5p in the aggressive progression of MM in vitro. We verified that miR-483-5p promoted MM cell proliferation and reduced apoptosis. Then we predicted and validated that TIMP2, a tumor suppressor gene, is the downstream target of miR-483-5p in MM. In summary, our study indicated that MM-MSCs promote MM malignant progression via the release of exosomes and regulation of miR-483-5p/TIMP2 axis, suggesting an essential role of BMSCs derived exosomal miRNA in MM and a potential marker for MM diagnosis and therapy.
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spelling pubmed-89212602022-03-16 Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2 Gu, Jianmei Wang, Maoye Wang, Xinfeng Li, Jiao Liu, Haiyan Lin, Zenghua Yang, Xi Zhang, Xu Liu, Hong Front Cell Dev Biol Cell and Developmental Biology Bone marrow-derived mesenchymal stem cell (BMSC) is one crucial component of the multiple myeloma (MM) microenvironment and supports the malignant progression of MM. Whether BMSCs act on MM cells via exosomes has not been well characterized. Herein, we used microarrays to screen out differentially expressed miRNAs in BMSCs from patients with MM (MM-MSCs) or benign diseases (BD-MSCs). We found that miR-483-5p was highly expressed in MM-MSCs, which may be transported through exosomes from MM-MSCs to MM cells to increase miR-483-5p expression in them. We then investigated the role and mechanism of miR-483-5p in the aggressive progression of MM in vitro. We verified that miR-483-5p promoted MM cell proliferation and reduced apoptosis. Then we predicted and validated that TIMP2, a tumor suppressor gene, is the downstream target of miR-483-5p in MM. In summary, our study indicated that MM-MSCs promote MM malignant progression via the release of exosomes and regulation of miR-483-5p/TIMP2 axis, suggesting an essential role of BMSCs derived exosomal miRNA in MM and a potential marker for MM diagnosis and therapy. Frontiers Media S.A. 2022-03-01 /pmc/articles/PMC8921260/ /pubmed/35300408 http://dx.doi.org/10.3389/fcell.2022.862524 Text en Copyright © 2022 Gu, Wang, Wang, Li, Liu, Lin, Yang, Zhang and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Gu, Jianmei
Wang, Maoye
Wang, Xinfeng
Li, Jiao
Liu, Haiyan
Lin, Zenghua
Yang, Xi
Zhang, Xu
Liu, Hong
Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2
title Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2
title_full Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2
title_fullStr Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2
title_full_unstemmed Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2
title_short Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2
title_sort exosomal mir-483-5p in bone marrow mesenchymal stem cells promotes malignant progression of multiple myeloma by targeting timp2
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921260/
https://www.ncbi.nlm.nih.gov/pubmed/35300408
http://dx.doi.org/10.3389/fcell.2022.862524
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