Deregulated WWOX is involved in a negative feedback loop with microRNA-214-3p in osteosarcoma.

WW domain-containing oxidoreductase (WWOX) is frequently inactivated in human osteosarcoma, and the restoration of its expression can suppress tumorigenicity in WWOX-negative OS cells. However, its regulatory mechanisms remain to be fully elucidated. In the present study, we demonstrate that WWOX is downregulated and that it regulates proliferation and epithelial-to-mesenchymal transition (EMT)-associated protein expression in osteosarcoma. As shown by our results, WWOX overexpression by transfection with WWOX overexpression plasmids suppressed the proliferation, migration and invasion of osteosarcoma MG63 cells (as shown by MTT and migration and invasion assays). The silencing of microRNA (miR)‑214‑3p by transfection with anti-miR‑14‑3p upregulated WWOX protein expression and also inhibited the proliferation, migration and invasion of osteosarcoma cells. Additionally, we found that WWOX negatively regulated miR‑214‑3p and miR‑10b expression. Our findings define a negative feedback pathway in control of WWOX and miR‑214‑3p expression, thus providing novel molecular targets for the treatment of osteosarcoma.