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miR-19 Promotes Cell Proliferation, Invasion, Migration, and EMT by Inhibiting SPRED2-mediated Autophagy in Osteosarcoma Cells

Osteosarcoma is an aggressive malignancy with rapid development and poor prognosis. microRNA-19 (miR-19) plays an important role in several biological processes. Sprouty-related EVH1 domain protein 2 (SPRED2) is a suppressor of extracellular signal-regulated kinase/mitogen-activated protein kinase (...

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Autores principales: Xie, Chuhai, Liu, Shengyao, Wu, Boyi, Zhao, Yu, Chen, Binwei, Guo, Jianhong, Qiu, ShouHong, Cao, Yan-ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784565/
https://www.ncbi.nlm.nih.gov/pubmed/33023313
http://dx.doi.org/10.1177/0963689720962460
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author Xie, Chuhai
Liu, Shengyao
Wu, Boyi
Zhao, Yu
Chen, Binwei
Guo, Jianhong
Qiu, ShouHong
Cao, Yan-ming
author_facet Xie, Chuhai
Liu, Shengyao
Wu, Boyi
Zhao, Yu
Chen, Binwei
Guo, Jianhong
Qiu, ShouHong
Cao, Yan-ming
author_sort Xie, Chuhai
collection PubMed
description Osteosarcoma is an aggressive malignancy with rapid development and poor prognosis. microRNA-19 (miR-19) plays an important role in several biological processes. Sprouty-related EVH1 domain protein 2 (SPRED2) is a suppressor of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling to inhibit tumor development and progression by promoting autophagy. In this study, we investigated the roles of miR-19, SPRED2, and autophagy in osteosarcoma. We detected the expression of miR-19, SPRED2, epithelial–mesenchymal transition (EMT) markers, and autophagy-related proteins via quantitative real-time polymerase chain reaction or western blot. To evaluate the function of miR-19 and SPRED2, we used MTT and colony formation assays to detect cell proliferation, Transwell, and wound-healing assays to detect cell invasion and migration. Targetscan and luciferase reporter assays confirmed the relationship between SPRED2 and miR-19. The expression of miR-19 was significantly upregulated in osteosarcoma, while SPRED2 was downregulated. miR-19 inhibitor reduced cell proliferation, invasion, migration, and EMT, while its cell biological effects were partially reversed by addition of autophagy inhibitor 3-methyladenine (3-MA) or SPRED2 siRNA in osteosarcoma. SPRED2, a suppressor of ERK/MAPK pathway that is known to trigger autophagy, was identified as a direct target of miR-19. SPRED2 overexpression increased cell proliferation, invasion, migration, and EMT by promoting autophagy, and the effects could be inhibited by 3-MA. Collectively, these findings reveal an underlying mechanism for development of osteosarcoma. miR-19 was upregulated in osteosarcoma cells, and negatively regulated SPRED2, thus promoting the malignant transformation of osteosarcoma cells via inhibiting SPRED2-induced autophagy. Therefore, miR-19/SPRED2 may be a potential target for the treatment of osteosarcoma.
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spelling pubmed-77845652021-01-14 miR-19 Promotes Cell Proliferation, Invasion, Migration, and EMT by Inhibiting SPRED2-mediated Autophagy in Osteosarcoma Cells Xie, Chuhai Liu, Shengyao Wu, Boyi Zhao, Yu Chen, Binwei Guo, Jianhong Qiu, ShouHong Cao, Yan-ming Cell Transplant Original Article Osteosarcoma is an aggressive malignancy with rapid development and poor prognosis. microRNA-19 (miR-19) plays an important role in several biological processes. Sprouty-related EVH1 domain protein 2 (SPRED2) is a suppressor of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling to inhibit tumor development and progression by promoting autophagy. In this study, we investigated the roles of miR-19, SPRED2, and autophagy in osteosarcoma. We detected the expression of miR-19, SPRED2, epithelial–mesenchymal transition (EMT) markers, and autophagy-related proteins via quantitative real-time polymerase chain reaction or western blot. To evaluate the function of miR-19 and SPRED2, we used MTT and colony formation assays to detect cell proliferation, Transwell, and wound-healing assays to detect cell invasion and migration. Targetscan and luciferase reporter assays confirmed the relationship between SPRED2 and miR-19. The expression of miR-19 was significantly upregulated in osteosarcoma, while SPRED2 was downregulated. miR-19 inhibitor reduced cell proliferation, invasion, migration, and EMT, while its cell biological effects were partially reversed by addition of autophagy inhibitor 3-methyladenine (3-MA) or SPRED2 siRNA in osteosarcoma. SPRED2, a suppressor of ERK/MAPK pathway that is known to trigger autophagy, was identified as a direct target of miR-19. SPRED2 overexpression increased cell proliferation, invasion, migration, and EMT by promoting autophagy, and the effects could be inhibited by 3-MA. Collectively, these findings reveal an underlying mechanism for development of osteosarcoma. miR-19 was upregulated in osteosarcoma cells, and negatively regulated SPRED2, thus promoting the malignant transformation of osteosarcoma cells via inhibiting SPRED2-induced autophagy. Therefore, miR-19/SPRED2 may be a potential target for the treatment of osteosarcoma. SAGE Publications 2020-10-06 /pmc/articles/PMC7784565/ /pubmed/33023313 http://dx.doi.org/10.1177/0963689720962460 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
Xie, Chuhai
Liu, Shengyao
Wu, Boyi
Zhao, Yu
Chen, Binwei
Guo, Jianhong
Qiu, ShouHong
Cao, Yan-ming
miR-19 Promotes Cell Proliferation, Invasion, Migration, and EMT by Inhibiting SPRED2-mediated Autophagy in Osteosarcoma Cells
title miR-19 Promotes Cell Proliferation, Invasion, Migration, and EMT by Inhibiting SPRED2-mediated Autophagy in Osteosarcoma Cells
title_full miR-19 Promotes Cell Proliferation, Invasion, Migration, and EMT by Inhibiting SPRED2-mediated Autophagy in Osteosarcoma Cells
title_fullStr miR-19 Promotes Cell Proliferation, Invasion, Migration, and EMT by Inhibiting SPRED2-mediated Autophagy in Osteosarcoma Cells
title_full_unstemmed miR-19 Promotes Cell Proliferation, Invasion, Migration, and EMT by Inhibiting SPRED2-mediated Autophagy in Osteosarcoma Cells
title_short miR-19 Promotes Cell Proliferation, Invasion, Migration, and EMT by Inhibiting SPRED2-mediated Autophagy in Osteosarcoma Cells
title_sort mir-19 promotes cell proliferation, invasion, migration, and emt by inhibiting spred2-mediated autophagy in osteosarcoma cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784565/
https://www.ncbi.nlm.nih.gov/pubmed/33023313
http://dx.doi.org/10.1177/0963689720962460
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