Objective: Novel therapeutic strategies are emerging with the increased understanding of the underlying mechanisms of human osteosarcoma. This current study tends to decipher the potentially critical role of DEP domain‐containing 1 (DEPDC1), a tumor‐related gene, during the progression of osteosarcoma.Methods: Bioinformatics analysis of 25,035 genes from the National Center for Biotechnology Information (NCBI) databases was performed to screen differentially expressed genes between osteosarcoma and normal control groups, complemented by the examination of 85 clinical osteosarcoma specimens. Furthermore, the manipulation ofDEPDC1expression levels by using silencing RNA (siRNA) or lentiviral vector intervention on human osteosarcoma cells was performed to reveal its role and interactions in in vitro and in vivo settings.Results: Gene expression profile analysis and immunohistochemical (IHC) examination suggested thatDEPDC1is highly expressed in human osteosarcoma cells and tumor tissue. The silencing ofDEPDC1arrested osteosarcoma cell proliferation, promoted apoptosis, and ceased tumor metastasis. Studies involving clinical human osteosarcoma cases exhibited a strong correlation ofDEPDC1over‐expressed osteosarcoma specimens with a reduced patient survival rate.Conclusions: Collectively, this study demonstrated thatDEPDC1is a critical driver in the promotion of osteosarcoma progression and results in poor patient prognosis. Genetically targeting or pharmacologically inhibitingDEPDC1may serve as a promising strategy for treating human osteosarcoma.

CD8⁺ T cell immune responses are regulated by multi-layer networks, while the post-translational regulation remains largely unknown. Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins. Here, by targeting the sheddase A Disintegrin and Metalloprotease (ADAM)17, we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8⁺ T cells. Transcriptomic and proteomic analysis revealed the involvement of post-translational regulation in CD8⁺ T cells. T cell-specific deletion of ADAM17 led to a dramatic increase in effector CD8⁺ T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors. Mechanistically, ADAM17 regulated CD8⁺ T cells through cleavage of membrane CD122. ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8⁺ T cells. Intriguingly, inhibition of ADAM17 in CD8⁺ T cells improved the efficacy of chimeric antigen receptor (CAR) T cells in solid tumors. Our findings reveal a critical post-translational regulation in CD8⁺ T cells, providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.

Aim: To investigate the effect of UBE2T gene on radiotherapy for osteosarcoma. Materials & methods: Gene Expression Omnibus database, RT-qPCR and immunohistochemical analysis were performed. Cell proliferation and cell cycle experiments were conducted after knockdown of UBE2T. Cell scratch, reactive oxygen species production and apoptosis experiments were conducted after the combination of radiotherapy and UBE2T silencing. Then the xenograft mode was further conducted. Results: UBE2T was highly expressed in human osteosarcoma. Suppression of UBE2T inhibited osteosarcoma cell proliferation and induced cell cycle arrest at the G2/M phase. Downregulation of UBE2T combined with radiation can substantially inhibit clonal formation and migration, and promote apoptosis of osteosarcoma cells in vitro and in vivo. Conclusion: UBE2T downregulation can enhance the radiosensitivity of osteosarcoma in vitro and in vivo.