TMED3/RPS15A Axis promotes the development and progression of osteosarcoma

Abstract Background Osteosarcoma is a primary malignant tumor that mainly affects children and young adults. Transmembrane emp24 trafficking protein 3 (TMED3) may be involved in the regulation of malignant cancer behaviors. However, the role of TMED3 in osteosarcoma remains mysterious. In this study...

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Autores principales:	Wei Xu, Yifan Li, Xiaojian Ye, Yunhan Ji, Yu Chen, Xiangyang Zhang, Zhikun Li
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Osteosarcoma TMED3 RPS15A Proliferation Apoptosis Migration Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/de3dae0345e242e9a125ea71ac557257
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spelling	oai:doaj.org-article:de3dae0345e242e9a125ea71ac5572572021-11-28T12:36:44ZTMED3/RPS15A Axis promotes the development and progression of osteosarcoma10.1186/s12935-021-02340-w1475-2867https://doaj.org/article/de3dae0345e242e9a125ea71ac5572572021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02340-whttps://doaj.org/toc/1475-2867Abstract Background Osteosarcoma is a primary malignant tumor that mainly affects children and young adults. Transmembrane emp24 trafficking protein 3 (TMED3) may be involved in the regulation of malignant cancer behaviors. However, the role of TMED3 in osteosarcoma remains mysterious. In this study, the potential biological function and underlying mechanism of TMED3 in progression of osteosarcoma was elaborated. Methods The expression of TMED3 in osteosarcoma was analyzed by immunohistochemical staining. The biological function of TMED3 in osteosarcoma was determined through loss-of-function assays in vitro. The effect of TMED3 downregulation on osteosarcoma was further explored by xenograft tumor model. The molecular mechanism of the regulation of TMED3 on osteosarcoma was determined by gene expression profile analysis. Results The expression of TMED3 in osteosarcoma tissues was significantly greater than that in matched adjacent normal tissues. Knockdown of TMED3 inhibited the progression of osteosarcoma by suppressing proliferation, impeding migration and enhancing apoptosis in vitro. We further validated that knockdown of TMED3 inhibited osteosarcoma generation in vivo. Additionally, ribosomal protein S15A (RPS15A) was determined as a potential downstream target for TMED3 involved in the progression of osteosarcoma. Further investigations elucidated that the simultaneous knockdown of RPS15A and TMED3 intensified the inhibitory effects on osteosarcoma cells. Importantly, knockdown of RPS15A alleviated the promotion effects of TMED3 overexpression in osteosarcoma cells. Conclusions In summary, these findings emphasized the importance of TMED3/RPS15A axis in promoting tumor progression, which may be a promising candidate for molecular therapy of osteosarcoma.Wei XuYifan LiXiaojian YeYunhan JiYu ChenXiangyang ZhangZhikun LiBMCarticleOsteosarcomaTMED3RPS15AProliferationApoptosisMigrationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Osteosarcoma TMED3 RPS15A Proliferation Apoptosis Migration Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Osteosarcoma TMED3 RPS15A Proliferation Apoptosis Migration Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Wei Xu Yifan Li Xiaojian Ye Yunhan Ji Yu Chen Xiangyang Zhang Zhikun Li TMED3/RPS15A Axis promotes the development and progression of osteosarcoma
description	Abstract Background Osteosarcoma is a primary malignant tumor that mainly affects children and young adults. Transmembrane emp24 trafficking protein 3 (TMED3) may be involved in the regulation of malignant cancer behaviors. However, the role of TMED3 in osteosarcoma remains mysterious. In this study, the potential biological function and underlying mechanism of TMED3 in progression of osteosarcoma was elaborated. Methods The expression of TMED3 in osteosarcoma was analyzed by immunohistochemical staining. The biological function of TMED3 in osteosarcoma was determined through loss-of-function assays in vitro. The effect of TMED3 downregulation on osteosarcoma was further explored by xenograft tumor model. The molecular mechanism of the regulation of TMED3 on osteosarcoma was determined by gene expression profile analysis. Results The expression of TMED3 in osteosarcoma tissues was significantly greater than that in matched adjacent normal tissues. Knockdown of TMED3 inhibited the progression of osteosarcoma by suppressing proliferation, impeding migration and enhancing apoptosis in vitro. We further validated that knockdown of TMED3 inhibited osteosarcoma generation in vivo. Additionally, ribosomal protein S15A (RPS15A) was determined as a potential downstream target for TMED3 involved in the progression of osteosarcoma. Further investigations elucidated that the simultaneous knockdown of RPS15A and TMED3 intensified the inhibitory effects on osteosarcoma cells. Importantly, knockdown of RPS15A alleviated the promotion effects of TMED3 overexpression in osteosarcoma cells. Conclusions In summary, these findings emphasized the importance of TMED3/RPS15A axis in promoting tumor progression, which may be a promising candidate for molecular therapy of osteosarcoma.
format	article
author	Wei Xu Yifan Li Xiaojian Ye Yunhan Ji Yu Chen Xiangyang Zhang Zhikun Li
author_facet	Wei Xu Yifan Li Xiaojian Ye Yunhan Ji Yu Chen Xiangyang Zhang Zhikun Li
author_sort	Wei Xu
title	TMED3/RPS15A Axis promotes the development and progression of osteosarcoma
title_short	TMED3/RPS15A Axis promotes the development and progression of osteosarcoma
title_full	TMED3/RPS15A Axis promotes the development and progression of osteosarcoma
title_fullStr	TMED3/RPS15A Axis promotes the development and progression of osteosarcoma
title_full_unstemmed	TMED3/RPS15A Axis promotes the development and progression of osteosarcoma
title_sort	tmed3/rps15a axis promotes the development and progression of osteosarcoma
publisher	BMC
publishDate	2021
url	https://doaj.org/article/de3dae0345e242e9a125ea71ac557257
work_keys_str_mv	AT weixu tmed3rps15aaxispromotesthedevelopmentandprogressionofosteosarcoma AT yifanli tmed3rps15aaxispromotesthedevelopmentandprogressionofosteosarcoma AT xiaojianye tmed3rps15aaxispromotesthedevelopmentandprogressionofosteosarcoma AT yunhanji tmed3rps15aaxispromotesthedevelopmentandprogressionofosteosarcoma AT yuchen tmed3rps15aaxispromotesthedevelopmentandprogressionofosteosarcoma AT xiangyangzhang tmed3rps15aaxispromotesthedevelopmentandprogressionofosteosarcoma AT zhikunli tmed3rps15aaxispromotesthedevelopmentandprogressionofosteosarcoma
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TMED3/RPS15A Axis promotes the development and progression of osteosarcoma

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