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ADAM10 promotes cell growth, migration, and invasion in osteosarcoma via regulating E-cadherin/β-catenin signaling pathway and is regulated by miR-122-5p
BACKGROUND: Osteosarcoma is a malignant bone tumor. Increasing evidences have revealed that a disintegrin and metalloproteinase 10 (ADAM10) is implicated in tumor development. The main purpose of this study is to explore the effects of ADAM10 on osteosarcoma cell functions and the underlying molecul...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106760/ https://www.ncbi.nlm.nih.gov/pubmed/32256208 http://dx.doi.org/10.1186/s12935-020-01174-2 |
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author | Yuan, Quan Yu, Honghao Chen, Jianhua Song, Xiaoyu Sun, Li |
author_facet | Yuan, Quan Yu, Honghao Chen, Jianhua Song, Xiaoyu Sun, Li |
author_sort | Yuan, Quan |
collection | PubMed |
description | BACKGROUND: Osteosarcoma is a malignant bone tumor. Increasing evidences have revealed that a disintegrin and metalloproteinase 10 (ADAM10) is implicated in tumor development. The main purpose of this study is to explore the effects of ADAM10 on osteosarcoma cell functions and the underlying molecular mechanisms. METHODS: Western blot and quantitative real-time PCR were performed to detect the expression of ADAM10 in one osteoblast (hFOB 1.19) and six osteosarcoma cells (Saos-2, SW1353, HOS, U-2OS, MG63, and 143B). The biological functions of ADAM10 in osteosarcoma cells were measured by cell counting kit-8 assay, flow cytometry, wound healing assay, and transwell assay. The interaction between miR-122-5p and ADAM10 was validated using dual-luciferase reporter assay. The effect of ADAM10 on the tumorigenicity of osteosarcoma cells was evaluated in a nude mice model in vivo. RESULTS: We found that the expression of ADAM10 was relatively high in osteosarcoma cells compared with that in osteoblast. ADAM10 promoted osteosarcoma cell growth, migration, and invasion. Mechanism studies showed that knockdown of ADAM10 inactivated E-cadherin/β-catenin signaling pathway, as evidenced by increased the level of E-cadherin, reduced nuclear translocation of β-catenin, and decreased the levels of MMP-9, Cyclin D1, c-Myc, and Survivin. Downregulation of ADAM10 suppressed the tumorigenicity of osteosarcoma cells in vivo. Furthermore, ADAM10 was validated to be a downstream target of microRNA-122-5p (miR-122-5p). MiR-122-5p-induced inhibition of cell proliferation, migration, and invasion was reversed by overexpression of ADAM10 in osteosarcoma cells. CONCLUSIONS: Collectively, the key findings of this study are that ADAM10 promotes osteosarcoma cell proliferation, migration, and invasion by regulating E-cadherin/β-catenin signaling pathway, and miR-122-5p can target ADAM10, indicating that miR-122-5p/ADAM10 axis might serve as a therapeutic target of osteosarcoma. |
format | Online Article Text |
id | pubmed-7106760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-71067602020-04-01 ADAM10 promotes cell growth, migration, and invasion in osteosarcoma via regulating E-cadherin/β-catenin signaling pathway and is regulated by miR-122-5p Yuan, Quan Yu, Honghao Chen, Jianhua Song, Xiaoyu Sun, Li Cancer Cell Int Primary Research BACKGROUND: Osteosarcoma is a malignant bone tumor. Increasing evidences have revealed that a disintegrin and metalloproteinase 10 (ADAM10) is implicated in tumor development. The main purpose of this study is to explore the effects of ADAM10 on osteosarcoma cell functions and the underlying molecular mechanisms. METHODS: Western blot and quantitative real-time PCR were performed to detect the expression of ADAM10 in one osteoblast (hFOB 1.19) and six osteosarcoma cells (Saos-2, SW1353, HOS, U-2OS, MG63, and 143B). The biological functions of ADAM10 in osteosarcoma cells were measured by cell counting kit-8 assay, flow cytometry, wound healing assay, and transwell assay. The interaction between miR-122-5p and ADAM10 was validated using dual-luciferase reporter assay. The effect of ADAM10 on the tumorigenicity of osteosarcoma cells was evaluated in a nude mice model in vivo. RESULTS: We found that the expression of ADAM10 was relatively high in osteosarcoma cells compared with that in osteoblast. ADAM10 promoted osteosarcoma cell growth, migration, and invasion. Mechanism studies showed that knockdown of ADAM10 inactivated E-cadherin/β-catenin signaling pathway, as evidenced by increased the level of E-cadherin, reduced nuclear translocation of β-catenin, and decreased the levels of MMP-9, Cyclin D1, c-Myc, and Survivin. Downregulation of ADAM10 suppressed the tumorigenicity of osteosarcoma cells in vivo. Furthermore, ADAM10 was validated to be a downstream target of microRNA-122-5p (miR-122-5p). MiR-122-5p-induced inhibition of cell proliferation, migration, and invasion was reversed by overexpression of ADAM10 in osteosarcoma cells. CONCLUSIONS: Collectively, the key findings of this study are that ADAM10 promotes osteosarcoma cell proliferation, migration, and invasion by regulating E-cadherin/β-catenin signaling pathway, and miR-122-5p can target ADAM10, indicating that miR-122-5p/ADAM10 axis might serve as a therapeutic target of osteosarcoma. BioMed Central 2020-03-30 /pmc/articles/PMC7106760/ /pubmed/32256208 http://dx.doi.org/10.1186/s12935-020-01174-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Yuan, Quan Yu, Honghao Chen, Jianhua Song, Xiaoyu Sun, Li ADAM10 promotes cell growth, migration, and invasion in osteosarcoma via regulating E-cadherin/β-catenin signaling pathway and is regulated by miR-122-5p |
title | ADAM10 promotes cell growth, migration, and invasion in osteosarcoma via regulating E-cadherin/β-catenin signaling pathway and is regulated by miR-122-5p |
title_full | ADAM10 promotes cell growth, migration, and invasion in osteosarcoma via regulating E-cadherin/β-catenin signaling pathway and is regulated by miR-122-5p |
title_fullStr | ADAM10 promotes cell growth, migration, and invasion in osteosarcoma via regulating E-cadherin/β-catenin signaling pathway and is regulated by miR-122-5p |
title_full_unstemmed | ADAM10 promotes cell growth, migration, and invasion in osteosarcoma via regulating E-cadherin/β-catenin signaling pathway and is regulated by miR-122-5p |
title_short | ADAM10 promotes cell growth, migration, and invasion in osteosarcoma via regulating E-cadherin/β-catenin signaling pathway and is regulated by miR-122-5p |
title_sort | adam10 promotes cell growth, migration, and invasion in osteosarcoma via regulating e-cadherin/β-catenin signaling pathway and is regulated by mir-122-5p |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106760/ https://www.ncbi.nlm.nih.gov/pubmed/32256208 http://dx.doi.org/10.1186/s12935-020-01174-2 |
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