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Orai1 Promotes Osteosarcoma Metastasis by Activating the Ras-Rac1-WAVE2 Signaling Pathway

BACKGROUND: The purpose of this study was to investigate whether Orai1 plays a role in the metastasis of osteosarcoma. MATERIAL/METHODS: The expression of Orai1 was silenced by small interfering RNAs against Orai1 (Orai1 siRNA) in osteosarcoma MG-63 cells. Various experiments were carried out to det...

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Autores principales: Guo, Yunshan, Zhu, Jinwen, Wang, Xiaodong, Li, Ruoyu, Jiang, Kuo, Chen, Shi, Fan, Jinzhu, Xue, Liujie, Hao, Dingjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909920/
https://www.ncbi.nlm.nih.gov/pubmed/31796725
http://dx.doi.org/10.12659/MSM.919594
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author Guo, Yunshan
Zhu, Jinwen
Wang, Xiaodong
Li, Ruoyu
Jiang, Kuo
Chen, Shi
Fan, Jinzhu
Xue, Liujie
Hao, Dingjun
author_facet Guo, Yunshan
Zhu, Jinwen
Wang, Xiaodong
Li, Ruoyu
Jiang, Kuo
Chen, Shi
Fan, Jinzhu
Xue, Liujie
Hao, Dingjun
author_sort Guo, Yunshan
collection PubMed
description BACKGROUND: The purpose of this study was to investigate whether Orai1 plays a role in the metastasis of osteosarcoma. MATERIAL/METHODS: The expression of Orai1 was silenced by small interfering RNAs against Orai1 (Orai1 siRNA) in osteosarcoma MG-63 cells. Various experiments were carried out to detect the changes in migration, invasion, and adhesion ability of these osteosarcoma cells. Furthermore, the activity of Rac1, Wave2, and Ras was detected using Western blot analysis. Moreover, the Rac1 and Ras inhibitors were used to confirm whether the Ras-Rac1-WAVE2 signaling pathway was involved in osteosarcoma metastasis promoted by Orai1. RESULTS: We found that the migration, invasion, and adhesion ability of MG-63 cells were significantly reduced after silencing Orai1 expression (p<0.05). Moreover, the activity of the Rac1-WAVE2 signaling pathway was significantly inhibited after silencing of Orai1 expression (p<0.05). After the Rac1 inhibitor was added, Orai1 siRNA could not further inhibit migration, invasion, and adhesion of the osteosarcoma cells. Further experiments showed that Ras activity was significantly inhibited after silencing Orai1 expression (p<0.05). Moreover, Orai1 siRNA did not further inhibit the activity of the Rac1-WAVE2 signaling pathway nor did it further inhibit the migration, invasion, and adhesion ability of osteosarcoma cells following the addition of Ras inhibitors. CONCLUSIONS: Orai1 activates the Ras-Rac1-WAVE2 signaling pathway to promote metastasis of osteosarcoma. Abnormal expression or function of Orai1 may be an important cause of osteosarcoma metastasis.
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spelling pubmed-69099202019-12-16 Orai1 Promotes Osteosarcoma Metastasis by Activating the Ras-Rac1-WAVE2 Signaling Pathway Guo, Yunshan Zhu, Jinwen Wang, Xiaodong Li, Ruoyu Jiang, Kuo Chen, Shi Fan, Jinzhu Xue, Liujie Hao, Dingjun Med Sci Monit Lab/In Vitro Research BACKGROUND: The purpose of this study was to investigate whether Orai1 plays a role in the metastasis of osteosarcoma. MATERIAL/METHODS: The expression of Orai1 was silenced by small interfering RNAs against Orai1 (Orai1 siRNA) in osteosarcoma MG-63 cells. Various experiments were carried out to detect the changes in migration, invasion, and adhesion ability of these osteosarcoma cells. Furthermore, the activity of Rac1, Wave2, and Ras was detected using Western blot analysis. Moreover, the Rac1 and Ras inhibitors were used to confirm whether the Ras-Rac1-WAVE2 signaling pathway was involved in osteosarcoma metastasis promoted by Orai1. RESULTS: We found that the migration, invasion, and adhesion ability of MG-63 cells were significantly reduced after silencing Orai1 expression (p<0.05). Moreover, the activity of the Rac1-WAVE2 signaling pathway was significantly inhibited after silencing of Orai1 expression (p<0.05). After the Rac1 inhibitor was added, Orai1 siRNA could not further inhibit migration, invasion, and adhesion of the osteosarcoma cells. Further experiments showed that Ras activity was significantly inhibited after silencing Orai1 expression (p<0.05). Moreover, Orai1 siRNA did not further inhibit the activity of the Rac1-WAVE2 signaling pathway nor did it further inhibit the migration, invasion, and adhesion ability of osteosarcoma cells following the addition of Ras inhibitors. CONCLUSIONS: Orai1 activates the Ras-Rac1-WAVE2 signaling pathway to promote metastasis of osteosarcoma. Abnormal expression or function of Orai1 may be an important cause of osteosarcoma metastasis. International Scientific Literature, Inc. 2019-12-04 /pmc/articles/PMC6909920/ /pubmed/31796725 http://dx.doi.org/10.12659/MSM.919594 Text en © Med Sci Monit, 2019 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Lab/In Vitro Research
Guo, Yunshan
Zhu, Jinwen
Wang, Xiaodong
Li, Ruoyu
Jiang, Kuo
Chen, Shi
Fan, Jinzhu
Xue, Liujie
Hao, Dingjun
Orai1 Promotes Osteosarcoma Metastasis by Activating the Ras-Rac1-WAVE2 Signaling Pathway
title Orai1 Promotes Osteosarcoma Metastasis by Activating the Ras-Rac1-WAVE2 Signaling Pathway
title_full Orai1 Promotes Osteosarcoma Metastasis by Activating the Ras-Rac1-WAVE2 Signaling Pathway
title_fullStr Orai1 Promotes Osteosarcoma Metastasis by Activating the Ras-Rac1-WAVE2 Signaling Pathway
title_full_unstemmed Orai1 Promotes Osteosarcoma Metastasis by Activating the Ras-Rac1-WAVE2 Signaling Pathway
title_short Orai1 Promotes Osteosarcoma Metastasis by Activating the Ras-Rac1-WAVE2 Signaling Pathway
title_sort orai1 promotes osteosarcoma metastasis by activating the ras-rac1-wave2 signaling pathway
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909920/
https://www.ncbi.nlm.nih.gov/pubmed/31796725
http://dx.doi.org/10.12659/MSM.919594
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