SNAI2 promotes the malignant transformation of oral leukoplakia by modulating p-EMT

Objective: Snail family transcriptional repressor 2 (SNAI2) is a key regulator of partial epithelial-mesenchymal transition (p-EMT) and is associated with tumorigenesis. Whether SNAI2 promotes oral leukoplakia (OLK) malignant transformation by modulating p-EMT is unclear.

Materials and methods: This study utilized two clinical datasets (GSE26549 and GSE85195) from the Gene Expression Omnibus database, cytological experiments, and a 4-nitroquinoline 1-oxide-induced mice model to explore the role of SNAI2 in OLK malignant transformation.

Results: The clinical cohort found SNAI2, as a risk factor (HR = 2.50, 95% CI: 1.08-5.79, p = 0.033), could promote OLK malignant transformation (p = 0.012). Cytological experiments indicated that SNAI2 overexpression promoted DOK cell proliferation, invasion, migration, and increase the protein expression of p-EMT relative signatures, whereas SNAI2 silencing has opposite effects. Furthermore, the mice model and clinical datasets demonstrated the expression of SNAI2 and p-EMT relative signatures were increased with OLK malignant transformation. And SNAI2 was strongly correlated with p-EMT. Besides, co-expressed genes of SNAI2 were also enriched in p-EMT relative biological processes and signaling pathways.

Conclusions: p-EMT plays a significant role in promoting the OLK malignant transformation. As an important regulator of p-EMT, SNAI2 could be a target to block the OLK malignant transformation.