LAUSR

Osteosarcoma (OS) is associated with a high incidence of lung metastasis, which leads to a high risk of cancer death. Circular RNA (circRNA), a novel class of noncoding RNA, is emerging as a key player in human cancer. Herein, we explored the role of circMGEA5 in OS metastasis by conducting circRNA expression microarray. CircMGEA5 was significantly upregulated in metastatic OS tissues compared to primary tissues. High circMGEA5 was positively related with shorter overall and disease‐free survival time. Knockdown of circMGEA5 suppressed OS cell migration, invasion, and epithelial–mesenchymal transition (EMT). Mechanistically, circMGEA5 acted as a competing endogenous RNA (ceRNA) to directly sponge miR‐153‐3p and miR‐8084, resulting in increasing ZEB1 and Snail expression, respectively, thereby inducing EMT and metastasis. In turn, ZEB1 and Snail were capable to bind to circMGEA5 promoter, activating circMGEA5 transcription, thus forming a positive feedback loop. Furthermore, we established the tail vein injection model and found that circMGEA5 depletion remarkably reduced lung metastasis nodules generated by OS cells. In sum, our findings, for the first time, reveal the metastasis‐promoting role of circMGEA5 in OS. Targeting of this newly identified ceRNA axis may be crucial in the development of novel therapies for metastatic OS patients.