MicroRNA-495 suppresses osteosarcoma invasion and migration by targeting HSP90AA1

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.www.impactjournals.com/oncotarget/

MiR-302c-5p affects the stemness and cisplatin resistance of nasopharyngeal carcinoma cells by regulating HSP90AA1

“…High HSP90 expression in patients with cancer may result in a poor prognosis and low survival rate [36]. Studies have shown that microRNA-495 inhibits the invasion and migration of osteosarcoma by targeting HSP90AA1 [37]. Similarly, our findings showed that miR-302c-5p targeted HSP90AA1.…”

“…As a molecular chaperone, HSP90 binds to various intracellular 'client proteins', such as EGFR, RAF-1, B-RAF and ERK1/2 AKT, HER2, EGFR and CDK4, to maintain their structural stability and activity [34][35][36][37]. Studies have shown that EGFR is a client protein of HSP90, and their interaction is critical for maintaining the stability of the receptor and for the growth of EGFR-dependent cancers [38].…”