Research Papers:
MicroRNA-495 suppresses osteosarcoma invasion and migration by targeting HSP90AA1
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Abstract
Xin Xiao1,*, Wei Wang2,*, Xiaokang Li1,*, Yuqian Li3, Di Yang1, Chao Shen1, Peng Gao1, Jie Wu1, Shuo Guo1 and Zheng Guo1
1Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
2Department of Immunology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
3Department 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: [email protected]
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.
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