TRIM21 knockdown suppresses ESCC progression and induces autophagy-mediated apoptosis via AKT/mTOR signaling pathway

Esophageal squamous cell carcinoma (ESCC) is a prevalent digestive tract malignancy characterized by high morbidity and mortality. Tripartite motif-containing protein 21 (TRIM21), a key regulator of innate immunity, has been implicated in the development of several cancers. However, its role in ESCC progression remains largely elusive. In this study, we identified TRIM21 as an oncogene promoting ESCC progression. Analysis of TCGA database revealed significant TRIM21 upregulation in ESCC tissues. In vitro, silencing TRIM21 markedly inhibited ESCC cell migration and invasion. Furthermore, TRIM21 downregulation substantially reduced cellular proliferation, associated with G1 phase cell cycle arrest and decreased CDK4/6 expression. We also observed that TRIM21 silencing significantly induced autophagy. This was evidenced by increased expression of autophagy-related markers (LC3B, Atg12, Beclin-1) and a higher number of autophagosomes and autolysosomes. Accompanied by autophagy, the apoptotic protein cleaved PARP1 (Cl. PARP1) in TRIM21 knockdown cells was raised. While the cells were treated with chloroquine (CQ), an autophagy inhibitor, the expression of Cl. PARP1 in the TRIM21 knockdown group was reduced compared to its control group. Mechanistically, TRIM21 loss inhibited the AKT/mTOR signaling pathway, thereby regulating cell growth and inducing autophagy-mediated apoptosis. Collectively, our findings provide novel insights into the role of TRIM21 in ESCC and offer a potential therapeutic target for ESCC.