Abstract
Osteosarcoma is a malignant tumor in children and adolescents. Previous studies showed that ATG4A is an autophagy-related gene involved in cancers. In this study, we aimed to identify the biological role of ATG4A in osteosarcoma. The expression levels of ATG4A were analyzed in osteosarcoma tissues by using reverse transcription-quantitative polymerase chain reaction (qRT-PCR) and western blotting. ATG4A was knocked-down or overexpressed in SAOS2 and HOS cell lines by transfection. Cell counting kit-8 (CCK-8) and clone formation assay were used to assess the effects of ATG4A on cell proliferation. Wound healing and Transwell assays were performed to evaluate the effects of ATG4A on cell migration and invasion, respectively. Epithelial-mesenchymal transition (EMT) markers and Notch signaling pathway targeting molecules were examined by western blotting. The results indicated that ATG4A was up-regulated in osteosarcoma tissues. In SAOS2 cells, knockdown of ATG4A inhibited the proliferation, migration and invasion, up-regulated the expression of E-cadherin and down-regulated the expression of vimentin, Notch1 and Hes1. In HOS cells, overexpression of ATG4A promoted the proliferation, migration and invasion, up-regulated the expression of vimentin, Notch1 and Hes1 and down-regulated the expression of E-cadherin. In conclusion, these findings demonstrate that ATG4A is up-regulated in osteosarcoma tissues. In osteosarcoma cells, ATG4A promotes the EMT process partly by the Notch signaling pathway. These results suggest that ATG4A might represent a potential therapeutic target for patients with osteosarcoma.