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// Xin Xiao 1, * , Wei Wang 2, * , Xiaokang Li 1, * , Yuqian Li 3 , Di Yang 1 , Chao Shen 1 , Peng Gao 1 , Jie Wu 1 , Shuo Guo 1 and Zheng Guo 1 1 Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China 2 Department of Immunology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China 3 Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China * These authors contributed equally to this work Correspondence to: Zheng Guo, email: guozheng@fmmu.edu.cn Keywords: osteosarcoma; metastasis; miR-495; HSP90AA1; PI3K/Akt/mTOR pathway Received: November 03, 2017 Accepted: January 03, 2018 Published: January 08, 2018 ABSTRACT MiR-495 is a tumor-suppressive microRNA that participates in tumor progression in human cancers. However, its expression and biological function in osteosarcoma remains unknown. In this study, we firstly found that miR-495 is markedly downregulated in both osteosarcoma tissues and cell lines. Then we demonstrated that miR-495 suppresses the invasion and metastasis of osteosarcoma cells in vitro through inhibiting epithelial to mesenchymal transition. Function of miR-495 in vivo was also examined in mice xenograft model and we found it significantly inhibiting the lung-metastasis of osteosarcoma cells. We also demonstrated that HSP90AA1 is a direct target of miR-495 using luciferase reporter assay and Western blot analysis. Furthermore, knockdown of HSP90AA1 can restore the increased cell invasion and migration in miR-495-knockdown cells and over expression of HSP90AA1 can neutralize the impaired metastatic ability of miR-495 mimic-treated cells. This metastasis-suppressive role of miR-495 in osteosarcoma is achieved by HSP90AA1-mediated PI3K/Akt/mTOR signaling pathway. Overall, our findings proved for the first time that miR-495 acts as a tumor suppressor in osteosarcoma and inhibits cell migration and invasion by targeting HSP90AA1, thus offering a promising therapeutic target for osteosarcoma treatment.

MicroRNA-495 suppresses osteosarcoma invasion and migration by targeting HSP90AA1