COPB2 drives gastric cancer progression via PI3K/AKT/NF-κB signaling: a multi-omics and functional study.

This study investigated the role of COPB2 in gastric cancer (GC) pathogenesis. Analysis of TCGA datasets and tissue microarrays revealed its upregulation in GC tissues compared to normal adjacent tissues, which was correlated with advanced tumor stage and lymphatic invasion and demonstrated significant diagnostic value (AUC = 0.895 and 0.851). Functional assays using lentiviral-mediated silencing in GC cells showed that COPB2 knockdown suppressed cell proliferation and migration, induced G0/G1-phase arrest, and promoted apoptosis. Mechanistic investigations through microarray, KEGG, and IPA analyses indicated that COPB2 dysregulation inactivated the PI3K/AKT and NF-κB signaling pathways. This led to the downregulation of key oncogenic effectors including Slug, FN1, CDH2, F2RL1, CDK6, CCND1, MMP9, CDKN2A, and SQSTM1, while upregulating tumor suppressors CDKN1B, CDKN1A, and DDIT3. In conclusion, COPB2 acts as an oncogene in GC, driving tumor progression through modulation of the cell cycle and key signaling pathways, highlighting its potential as a therapeutic target.