Abstract
Cancer cells have developed anoikis resistance and thereby survive after detachment from their primary site and while traveling through the circulation. However, the mechanisms underlying resistance to anoikis in osteosarcoma (OS) remain largely unknown. MicroRNAs (miRNA) have been reported to contribute to malignant phenotypes of cancer cells. To investigate the roles of miRNAs in anoikis resistance of OS cells, the implications of 9 well-characterized miRNAs that dysregulated in OS on cell anoikis were screened. As a result, miR-451 was identified as a crucial factor involved in anoikis resistance and anchorage-independent growth of OS cell. MiR-451 was down-regulated in OS cells, re-expression of miR-451 significantly promoted cell anoikis of three OS cell lines and inhibition of miR-451 protected HOS cells from anoikis under anoikis condition. Subsequently, bioinformatics prediction and luciferase reporter assay indicated that Rab14 was a direct target of miR-451, and Rab14 could be down-regulated by miR-451 at both mRNA and protein levels. Genetic silencing of Rab14 recapitulated the role of miR-451 on anoikis resistance and restoration of Rab14 largely abrogated the tumor suppressor function of miR-451. Finally, overexpression of miR-451 remarkably suppressed the lung metastasis of OS cells. Collectively, our findings suggest that the miR-451/Rab14 axis might serve as a novel mechanism of resistance to anoikis in OS.