Abstract
Gastric cancer (GC) remains a lethal malignancy with limited therapeutic options. We investigated the role of γ-actin (ACTG1) in GC progression. Bioinformatics analyses revealed that ACTG1 is upregulated in GC tissues and correlates with poor patient prognosis. Functionally, the knockdown of ACTG1 suppressed GC cell proliferation and metastasis in both in vitro and in vivo models. Transcriptomic sequencing identified COL21A1 as a key downstream effector, and KEGG analysis indicated involvement in epithelial-mesenchymal transition (EMT). Critically, overexpression of COL21A1 rescued the inhibitory effects of ACTG1 knockdown on proliferation, migration, and EMT. These findings demonstrate that the ACTG1/COL21A1 axis promotes GC progression by regulating EMT, highlighting its potential as a therapeutic target for patients with GC.