DEPDC1/ EEF1A1 complex promotes the progression of human osteosarcoma via downregulation of FOXO3a

Abstract

There are currently lack of effective therapeutic strategies for osteosarcoma, primarily due to insufficient understanding of the underlying mechanisms of the tumor cells. This study deciphers a potentially critical interplay of DEPDC1-EEF1A1-FOXO3a axis during the osteosarcoma progression. Bioinformatics analysis of documented 25,035 genes for differentially expressed genes were accompanied by transcriptional and translational examinations of clinical osteosarcoma specimens and osteosarcoma cell lines to assess the roles and interactions of DEP domain-containing 1 (DEPDC1), Elongation Factor 1-alpha 1 (EEF1A1), and FOXO3a in the tumor cells proliferation and prognosis. Gene expression profile analysis and clinical tests revealed highly expressed DEPDC1 in human osteosarcoma cells and tumor tissues. Vector-mediated silence of DEPDC1 resulted in halted osteosarcoma cell proliferation, promoted apoptosis, and ceased tumor metastasis. Immunoprecipitation assay confirmed that EEF1A1 directly bind to DEPDC1 protein through three binding regions. Further, DEPDC1/EEF1A1 complex significantly decreased the expression of FOXO3a at transcription and translation levels, which subsequently promoted the proliferation of osteosarcoma cells and tumor metastasis. Correlation studies exhibited that overexpression of DEPDC1/EEF1A1 complex in the clinical specimens negatively correlated with the patient survival rate. In conclusion, DEPDC1-EEF1A1-FOXO3a axis plays as a critical pathway that regulates the progression and prognosis of osteosarcoma.