miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3

BackgroundMicroRNAs are known to regulate carcinogenesis of osteosarcoma. Although, miR-16-5p is known to exert inhibitory effects on several forms of cancers, its effects on the growth and invasion of osteosarcoma have not been studied.MethodsWe collected human osteosarcoma specimens and adjacent t...

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Main Authors: Zhijian Gu, Zhikun Li, Ruijun Xu, Xiaodong Zhu, Ruixi Hu, Yonghua Xue, Wei Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-08-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2020.01324/full
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author Zhijian Gu
Zhikun Li
Ruijun Xu
Xiaodong Zhu
Ruixi Hu
Yonghua Xue
Wei Xu
author_facet Zhijian Gu
Zhikun Li
Ruijun Xu
Xiaodong Zhu
Ruixi Hu
Yonghua Xue
Wei Xu
author_sort Zhijian Gu
collection DOAJ
description BackgroundMicroRNAs are known to regulate carcinogenesis of osteosarcoma. Although, miR-16-5p is known to exert inhibitory effects on several forms of cancers, its effects on the growth and invasion of osteosarcoma have not been studied.MethodsWe collected human osteosarcoma specimens and adjacent tissues to detect the expression of miR-16-5p by real-time polymerase chain reaction, immunoblotting, and immunohistochemistry. The proliferation, migration, and invasion of MG63 and HOS cells following miR-16-5p overexpression and inhibition were detected with cell counting kit-8, wound healing assay, and Transwell assay, respectively. An expression vector carrying a mutated 3′-untranslated region of mothers against decapentaplegic homolog 3 (Smad3) was constructed.ResultsThe results showed that miR-16-5p expression was downregulated in osteosarcoma tissues and cells as compared with adjacent counterparts, while Smad3 was overexpressed in osteosarcoma cells. The overexpression of miR-16-5p resulted in the inhibition of the proliferation, migration, and invasion of osteosarcoma cells and enhanced the therapeutic effect of cisplatin. These effects were attenuated with miR-16-5p expression inhibition. In cells transfected with miR-16-5p mimic, Smad3 expression decreased, while this effect was absent in the cells carrying mutated Smad3.ConclusionsTherefore, miR-16-5p inhibits the growth and invasion of osteosarcoma by targeting Smad3.
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spelling doaj.art-ef547cb5c95144289a2abdaebd6373292022-12-22T00:01:01ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-08-011110.3389/fphar.2020.01324534070miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3Zhijian Gu0Zhikun Li1Ruijun Xu2Xiaodong Zhu3Ruixi Hu4Yonghua Xue5Wei Xu6Department of Orthopedics, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Orthopedics, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Orthopedics, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Orthopedics, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Orthopedics, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Neurosurgery, Putuo District Central Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Orthopedics, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaBackgroundMicroRNAs are known to regulate carcinogenesis of osteosarcoma. Although, miR-16-5p is known to exert inhibitory effects on several forms of cancers, its effects on the growth and invasion of osteosarcoma have not been studied.MethodsWe collected human osteosarcoma specimens and adjacent tissues to detect the expression of miR-16-5p by real-time polymerase chain reaction, immunoblotting, and immunohistochemistry. The proliferation, migration, and invasion of MG63 and HOS cells following miR-16-5p overexpression and inhibition were detected with cell counting kit-8, wound healing assay, and Transwell assay, respectively. An expression vector carrying a mutated 3′-untranslated region of mothers against decapentaplegic homolog 3 (Smad3) was constructed.ResultsThe results showed that miR-16-5p expression was downregulated in osteosarcoma tissues and cells as compared with adjacent counterparts, while Smad3 was overexpressed in osteosarcoma cells. The overexpression of miR-16-5p resulted in the inhibition of the proliferation, migration, and invasion of osteosarcoma cells and enhanced the therapeutic effect of cisplatin. These effects were attenuated with miR-16-5p expression inhibition. In cells transfected with miR-16-5p mimic, Smad3 expression decreased, while this effect was absent in the cells carrying mutated Smad3.ConclusionsTherefore, miR-16-5p inhibits the growth and invasion of osteosarcoma by targeting Smad3.https://www.frontiersin.org/article/10.3389/fphar.2020.01324/fullosteosarcomamiR-16-5pinvasionSmad3proliferation
spellingShingle Zhijian Gu
Zhikun Li
Ruijun Xu
Xiaodong Zhu
Ruixi Hu
Yonghua Xue
Wei Xu
miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3
Frontiers in Pharmacology
osteosarcoma
miR-16-5p
invasion
Smad3
proliferation
title miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3
title_full miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3
title_fullStr miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3
title_full_unstemmed miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3
title_short miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3
title_sort mir 16 5p suppresses progression and invasion of osteosarcoma via targeting at smad3
topic osteosarcoma
miR-16-5p
invasion
Smad3
proliferation
url https://www.frontiersin.org/article/10.3389/fphar.2020.01324/full
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