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04 December 2019 : Laboratory Research  

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

Yunshan Guo1A*, Jinwen Zhu1B, Xiaodong Wang1C, Ruoyu Li1C, Kuo Jiang1D, Shi Chen2F, Jinzhu Fan3E, Liujie Xue1F, Dingjun Hao1AG

DOI: 10.12659/MSM.919594

Med Sci Monit 2019; 25:9227-9236

Abstract

BACKGROUND: The purpose of this study was to investigate whether Orai1 plays a role in the metastasis of osteosarcoma.

MATERIAL AND 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.

Keywords: Genes, ras, Neoplasm Metastasis, Osteosarcoma, rac1 GTP-Binding Protein, Antineoplastic Agents, Bone Neoplasms, Cell Adhesion, Cell Movement, Neoplasm Invasiveness, ORAI1 Protein, RNA, Small Interfering, Signal Transduction, Wiskott-Aldrich Syndrome Protein Family, ras Proteins

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750