Knockdown of STAT1 inhibits epithelial–mesenchymal transition and attenuates the migration of nasopharyngeal carcinoma cells

Objective To investigate the expression pattern and functional role of signal transducer and activator of transcription 1 (STAT1) in nasopharyngeal carcinoma (NPC), focusing on epithelial-mesenchymal transition (EMT) and cellular motility. Methods High-throughput RNA sequencing (RNA-seq) of 4 NPC and 3 non-cancerous nasopharyngeal tissues identified differentially expressed genes (DEGs), followed by Gene Ontology (GO) and KEGG pathway enrichment analyses. STAT1 in situ expression was verified by immunohistochemistry (IHC) in paired clinical specimens. Stable STAT1-knockdown models were established in human 6-10B NPC cells using lentiviral shRNAs, with silencing efficiency confirmed via Western blotting. Protein levels of core EMT markers (N-cadherin, Snail, Vimentin, β-catenin, α-SMA, and E-cadherin) were evaluated, and two-dimensional cellular motility was assessed using real-time scratch wound healing assays (0–96 h). Results Transcriptomic profiling revealed 6,394 DEGs significantly enriched in cell adhesion and junction remodeling pathways. IHC confirmed prominent cytoplasmic and nuclear STAT1 overexpression in NPC tissues. Western blotting verified potent STAT1 knockdown (sh1: ~52.0% of NC, P< 0.05). STAT1 silencing significantly downregulated mesenchymal markers—including N-cadherin (P< 0.001), Snail (P< 0.0001), Vimentin (P< 0.01), β-catenin (P< 0.001), and α-SMA (P< 0.001)—without altering epithelial E-cadherin levels (P > 0.05). Consistently, STAT1 depletion markedly decelerated wound closure rates across 24 to 96 h compared to Mock controls (P< 0.05 or P< 0.01). Conclusion STAT1 is aberrantly overexpressed in NPC. Targeting STAT1 attenuates mesenchymal phenotypic traits, EMT-associated molecular programs, and cell motility, identifying STAT1 as a candidate molecular vulnerability that warrants further preclinical evaluation.