Identification and validation of programmed cell death-related genes in osteosarcoma: inhibiting CIB1 as a promising therapeutic strategy

This study explores programmed cell death (PCD)-related genes in osteosarcoma through bioinformatics and experimental validation. Analysis of datasets from the GEO and TCGA databases identified 5,327 differentially expressed genes (DEGs), among which 294 overlapped with PCD-related genes. LASSO regression analysis identified six hub genes, and five of these (CIB1, CREB3L1, IL6R, TGFβ2, and TNFRSF10C) were further validated in osteosarcoma tissues. Notably, CIB1 exhibited significantly elevated expression and was selected for in-depth analysis. CIB1 downregulation inhibited osteosarcoma cell proliferation and invasion by inducing apoptosis and causing G2/M phase cell cycle arrest, and was associated with increased p53 expression, decreased phosphorylation of Akt and STAT3, and altered BCL2/BAX ratios, suggesting involvement of these pathways in the observed effects. In vitro experiments confirmed the tumor-suppressive role of CIB1 inhibition. These findings highlight CIB1 as a promising therapeutic target for osteosarcoma treatment.