Knockdown of IGF2BP2 Inhibits THBS1 in Regulating the Progression of Oral Squamous Cell Carcinoma: An Integrative...

Oral squamous cell carcinoma (OSCC) begins with pre-existing oral potential malignant diseases (OP-MDs), among which oral leukoplakia (OL) is the most common precancerous lesion. This study systematically explored the mechanism of N6-methyladenosine (m6A) RNA methylation in the occurrence and development of OSCC by integrating bioinformatics analysis and experimental verification. Based on the analysis of the GSE85195 dataset, we identified the key differentially expressed genes (DEGs) and m6A regulatory factors in the progression from OL to OSCC. Functional enrichment analysis revealed that these genes were significantly enriched in the extracellular matrix (ECM) signaling pathway. By constructing a protein-protein interaction network, we identified THBS1 as the core hub gene, and survival analysis revealed that the high expression of THBS1 was associated with a poor prognosis of OSCC patients. Bioinformatics analysis found that IGF2BP2 could regulate the expression of THBS1 through m6A. In vitro assays indicated that IGF2BP2 can regulate the expression of THBS1, and knockdown of IGF2BP2 can significantly inhibit the proliferation, migration, and invasion abilities of OSCC cells. Further analysis revealed that the risk score based on IGF2BP2, THBS1, and tumor stage was closely associated with tumor immune microenvironment characteristics. These evidences not only reveal a potential new mechanism by which m6A modification may mediate the IGF2BP2-THBS1 axis to promote the progression of OSCC, but also provide a new theoretical basis for understanding the remodeling of the immune microenvironment of OSCC.