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Extracellular vesicles from bone mesenchymal stem cells transport microRNA-206 into osteosarcoma cells and target NRSN2 to block the ERK1/2-Bcl-xL signaling pathway
Osteosarcoma (OS) is a kind of malignant tumor originating from mesenchymal tissues. Bone mesenchymal stem cells-derived extracellular vesicles (BMSCs-EVs) can play important roles in OS. This study investigated the mechanism of BMSCs-EVs on OS. BMSC surface antigens and adipogenic and osteogenic di...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PAGEPress Publications, Pavia, Italy
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251612/ https://www.ncbi.nlm.nih.gov/pubmed/35730574 http://dx.doi.org/10.4081/ejh.2022.3394 |
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author | Keremu, Alimu Aila, Pazila Tusun, Aikebaier Abulikemu, Maimaitiaili Zou, Xiaoguang |
author_facet | Keremu, Alimu Aila, Pazila Tusun, Aikebaier Abulikemu, Maimaitiaili Zou, Xiaoguang |
author_sort | Keremu, Alimu |
collection | PubMed |
description | Osteosarcoma (OS) is a kind of malignant tumor originating from mesenchymal tissues. Bone mesenchymal stem cells-derived extracellular vesicles (BMSCs-EVs) can play important roles in OS. This study investigated the mechanism of BMSCs-EVs on OS. BMSC surface antigens and adipogenic and osteogenic differentiation were detected by flow cytometry, and oil red O and alizarin red staining. EVs were isolated from BMSCs by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot (WB). miR-206 and neurensin-2 (NRSN2) levels in human osteoblast hFOB 1.19 or OS cells (143B, MG-63, Saos2, HOS) were detected by RT-qPCR. Human OS cells with lower miR-206 levels were selected and treated with BMSCs-EVs or pSUPER-NRSN2. The uptake of EVs by 143B cells, cell proliferation, apoptosis, invasion, and migration were detected by immunofluorescence, 5-ethynyl-2’-deoxyuridine (EdU) and colony formation assays, flow cytometry, scratch test, and transwell assays. The binding sites between miR-206 and NRSN2 were predicted by Starbase database and verified by dual-luciferase assay. The OS xenograft model was established and treated with BMSCs-EVs. Tumor growth rate and volume, cell proliferation, and p-ERK1/2, ERK1/2, and Bcl-xL levels were detected by vernier caliper, immunohistochemistry, and WB. BMSCs-EVs were successfully extracted. miR-206 was diminished and NRSN2 was promoted in OS cells. BMSCs-EVs inhibited proliferation, migration, and invasion, and promoted apoptosis of OS cells. BMSCs-EVs carried miR-206 into OS cells. Inhibition of miR-206 in EVs partially reversed the inhibitory effect of EVs on malignant behaviors of OS cells. miR-206 targeted NRSN2. Overexpression of NRSN2 reversed the inhibitory effect of EVs on OS cells. NRSN2 activated the ERK1/2-Bcl-xL pathway. BMSC-EVs inhibited OS growth in vivo. In summary, BMSC-EVs targeted NRSN2 and inhibited the ERK1/2-Bcl-xL pathway by carrying miR-206 into OS cells, thus inhibiting OS progression. |
format | Online Article Text |
id | pubmed-9251612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | PAGEPress Publications, Pavia, Italy |
record_format | MEDLINE/PubMed |
spelling | pubmed-92516122022-07-05 Extracellular vesicles from bone mesenchymal stem cells transport microRNA-206 into osteosarcoma cells and target NRSN2 to block the ERK1/2-Bcl-xL signaling pathway Keremu, Alimu Aila, Pazila Tusun, Aikebaier Abulikemu, Maimaitiaili Zou, Xiaoguang Eur J Histochem Article Osteosarcoma (OS) is a kind of malignant tumor originating from mesenchymal tissues. Bone mesenchymal stem cells-derived extracellular vesicles (BMSCs-EVs) can play important roles in OS. This study investigated the mechanism of BMSCs-EVs on OS. BMSC surface antigens and adipogenic and osteogenic differentiation were detected by flow cytometry, and oil red O and alizarin red staining. EVs were isolated from BMSCs by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot (WB). miR-206 and neurensin-2 (NRSN2) levels in human osteoblast hFOB 1.19 or OS cells (143B, MG-63, Saos2, HOS) were detected by RT-qPCR. Human OS cells with lower miR-206 levels were selected and treated with BMSCs-EVs or pSUPER-NRSN2. The uptake of EVs by 143B cells, cell proliferation, apoptosis, invasion, and migration were detected by immunofluorescence, 5-ethynyl-2’-deoxyuridine (EdU) and colony formation assays, flow cytometry, scratch test, and transwell assays. The binding sites between miR-206 and NRSN2 were predicted by Starbase database and verified by dual-luciferase assay. The OS xenograft model was established and treated with BMSCs-EVs. Tumor growth rate and volume, cell proliferation, and p-ERK1/2, ERK1/2, and Bcl-xL levels were detected by vernier caliper, immunohistochemistry, and WB. BMSCs-EVs were successfully extracted. miR-206 was diminished and NRSN2 was promoted in OS cells. BMSCs-EVs inhibited proliferation, migration, and invasion, and promoted apoptosis of OS cells. BMSCs-EVs carried miR-206 into OS cells. Inhibition of miR-206 in EVs partially reversed the inhibitory effect of EVs on malignant behaviors of OS cells. miR-206 targeted NRSN2. Overexpression of NRSN2 reversed the inhibitory effect of EVs on OS cells. NRSN2 activated the ERK1/2-Bcl-xL pathway. BMSC-EVs inhibited OS growth in vivo. In summary, BMSC-EVs targeted NRSN2 and inhibited the ERK1/2-Bcl-xL pathway by carrying miR-206 into OS cells, thus inhibiting OS progression. PAGEPress Publications, Pavia, Italy 2022-06-22 /pmc/articles/PMC9251612/ /pubmed/35730574 http://dx.doi.org/10.4081/ejh.2022.3394 Text en ©Copyright: the Author(s) https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Article Keremu, Alimu Aila, Pazila Tusun, Aikebaier Abulikemu, Maimaitiaili Zou, Xiaoguang Extracellular vesicles from bone mesenchymal stem cells transport microRNA-206 into osteosarcoma cells and target NRSN2 to block the ERK1/2-Bcl-xL signaling pathway |
title | Extracellular vesicles from bone mesenchymal stem cells transport microRNA-206 into osteosarcoma cells and target NRSN2 to block the ERK1/2-Bcl-xL signaling pathway |
title_full | Extracellular vesicles from bone mesenchymal stem cells transport microRNA-206 into osteosarcoma cells and target NRSN2 to block the ERK1/2-Bcl-xL signaling pathway |
title_fullStr | Extracellular vesicles from bone mesenchymal stem cells transport microRNA-206 into osteosarcoma cells and target NRSN2 to block the ERK1/2-Bcl-xL signaling pathway |
title_full_unstemmed | Extracellular vesicles from bone mesenchymal stem cells transport microRNA-206 into osteosarcoma cells and target NRSN2 to block the ERK1/2-Bcl-xL signaling pathway |
title_short | Extracellular vesicles from bone mesenchymal stem cells transport microRNA-206 into osteosarcoma cells and target NRSN2 to block the ERK1/2-Bcl-xL signaling pathway |
title_sort | extracellular vesicles from bone mesenchymal stem cells transport microrna-206 into osteosarcoma cells and target nrsn2 to block the erk1/2-bcl-xl signaling pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251612/ https://www.ncbi.nlm.nih.gov/pubmed/35730574 http://dx.doi.org/10.4081/ejh.2022.3394 |
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