LAUSR

Decorin (DCN), a multifunctional extracellular matrix protein, has been reported to exhibit tumor‐suppressive effects in various cancers, including liver cancer. However, the transcriptional regulatory mechanisms of DCN in liver cancer remains unclear. We analyzed DCN expression in liver cancer cells using qPCR and Western blot. Functional assays (CCK‐8, colony formation, flow cytometry, and Transwell) were performed to assess the effects of DCN overexpression (via pcDNA3.1‐DCN) on proliferation, apoptosis, invasion, and migration. Bioinformatics tools (PROMO and UCSC) predicted EGR3 as a potential transcriptional regulator of DCN, which was validated through ChIP and luciferase reporter assays. Rescue experiments (si‐EGR3+pcDNA3.1‐DCN cotransfection) were conducted to confirm the DCN‐EGR3 regulatory axis. DCN was significantly downregulated in liver cancer cells. Its overexpression suppressed proliferation, invasion, and migration while promoting apoptosis. Mechanistically, EGR3 was identified as a transcriptional activator of DCN, and EGR3 knockdown reversed the tumor‐suppressive effects of DCN. Our findings demonstrated that DCN exerted antitumor effects in liver cancer via transcriptional activation by EGR3, providing a novel therapeutic target for liver cancer treatment.