Modulation of EMT-related gene expression in colorectal cancer by carvacrol-conjugated ZnO nanoparticles: an integrated in silico and in vitro study

Epithelial-to-mesenchymal transition (EMT) is a key driver of colorectal cancer (CRC) progression and metastasis. Identifying pivotal EMT-related genes and novel therapeutic approaches may enhance patient outcomes. In this study, we analyzed EMT-related gene expression in CRC using TCGA data and identified differentially expressed genes via protein-protein interaction networks and centrality analysis. The anticancer effects of ZnO and ZnO@glu-Carvacrol nanoparticle were evaluated in HCT-116 and HT-29 cells using MTT assays, gene expression profiling of proliferation and apoptosis markers, colony formation, and scratch wound-healing assays. Among 200 EMT-related genes, 75 were upregulated and 69 downregulated in CRC. Seventeen hub genes were identified, with SERPINE1 and BGN showing the strongest association with poor patient survival in exploratory survival analyses. Structural and morphological characterization confirmed that ZnO@Glu-Carva NP are crystalline nanocomposites with efficient Carvacrol loading and favorable physicochemical properties for biological applications. Treatment with ZnO@Glu-Carva NP (10 µg/mL) markedly reduced cell viability, suppressed CCND1 , CCNE1 , and BCL2 expression, upregulated BAX , and inhibited colony formation and wound closure. Notably, ZnO@Glu-Carva NP also significantly downregulated SERPINE1 and BGN expression in CRC cells. Our findings indicate that ZnO@Glu-Carva NP exert enhanced anticancer effects in CRC by modulating key EMT-related genes, promoting apoptosis, and impairing clonogenic growth and wound closure-associated cell motility. These results highlight their potential as a nanocomposite platform for further investigation in CRC therapeutic research.