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Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF

Osteosarcoma is the most common primary malignant tumor of bone derived from osteoblasts, which is a noteworthy threat to the health of children and adolescents. In this study, we found that MCM8 has significantly higher expression level in osteosarcoma tissues in comparison with normal tissues, whi...

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Autores principales: Ren, Zhinan, Li, Jun, Zhao, Shanwen, Qiao, Qi, Li, Runguang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027380/
https://www.ncbi.nlm.nih.gov/pubmed/33828075
http://dx.doi.org/10.1038/s41419-021-03621-y
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author Ren, Zhinan
Li, Jun
Zhao, Shanwen
Qiao, Qi
Li, Runguang
author_facet Ren, Zhinan
Li, Jun
Zhao, Shanwen
Qiao, Qi
Li, Runguang
author_sort Ren, Zhinan
collection PubMed
description Osteosarcoma is the most common primary malignant tumor of bone derived from osteoblasts, which is a noteworthy threat to the health of children and adolescents. In this study, we found that MCM8 has significantly higher expression level in osteosarcoma tissues in comparison with normal tissues, which was also correlated with more advanced tumor grade and pathological stage. In agreement with the role of MCM proteins as indicators of cell proliferation, knockdown/overexpression of MCM8 inhibited/promoted osteosarcoma cell proliferation in vitro and tumor growth in vivo. Also, MCM8 knockdown/overexpression was also significantly associated with the promotion/inhibition of cell apoptosis and suppression/promotion of cell migration. More importantly, mechanistic study identified CTGF as a potential downstream target of MCM8, silencing of which could enhance the regulatory effects of MCM8 knockdown and alleviate the effects of MCM8 overexpression on osteosarcoma development. In summary, MCM8/CTGF axis was revealed as critical participant in the development and progression of osteosarcoma and MCM8 may be a promising therapeutic target for osteosarcoma treatment.
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spelling pubmed-80273802021-04-21 Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF Ren, Zhinan Li, Jun Zhao, Shanwen Qiao, Qi Li, Runguang Cell Death Dis Article Osteosarcoma is the most common primary malignant tumor of bone derived from osteoblasts, which is a noteworthy threat to the health of children and adolescents. In this study, we found that MCM8 has significantly higher expression level in osteosarcoma tissues in comparison with normal tissues, which was also correlated with more advanced tumor grade and pathological stage. In agreement with the role of MCM proteins as indicators of cell proliferation, knockdown/overexpression of MCM8 inhibited/promoted osteosarcoma cell proliferation in vitro and tumor growth in vivo. Also, MCM8 knockdown/overexpression was also significantly associated with the promotion/inhibition of cell apoptosis and suppression/promotion of cell migration. More importantly, mechanistic study identified CTGF as a potential downstream target of MCM8, silencing of which could enhance the regulatory effects of MCM8 knockdown and alleviate the effects of MCM8 overexpression on osteosarcoma development. In summary, MCM8/CTGF axis was revealed as critical participant in the development and progression of osteosarcoma and MCM8 may be a promising therapeutic target for osteosarcoma treatment. Nature Publishing Group UK 2021-04-07 /pmc/articles/PMC8027380/ /pubmed/33828075 http://dx.doi.org/10.1038/s41419-021-03621-y Text en © The Author(s) 2021 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ren, Zhinan
Li, Jun
Zhao, Shanwen
Qiao, Qi
Li, Runguang
Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF
title Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF
title_full Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF
title_fullStr Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF
title_full_unstemmed Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF
title_short Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF
title_sort knockdown of mcm8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating ctgf
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027380/
https://www.ncbi.nlm.nih.gov/pubmed/33828075
http://dx.doi.org/10.1038/s41419-021-03621-y
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