CEACAM1 regulates autophagy in oral squamous cell carcinoma through the PPAR signaling pathway

Oral squamous cell carcinoma (OSCC), as one of the most common malignant tumors in the head and neck region, has a complex and diverse pathogenesis. An increasing number of studies indicate that cellular autophagy plays a significant role in the occurrence, development, and treatment of tumors. However, the specific mechanisms of autophagy in oral squamous cell carcinoma are not yet fully understood.

This study is based on the oral squamous cell carcinoma dataset GSE222673, and has conducted a gene set enrichment analysis (GSEA) on the whole genome, aiming to find potential enriched pathways among non-differentially expressed genes. Weighted gene co-expression network analysis (WGCNA) was used to identify key modules and determine the key hub genes within the modules. The experimental part employed Western Blot to verify the expression changes and functional roles of core molecules in OSCC cells.

GSEA indicates that non-differentially expressed genes are enriched in mitochondrial autophagy, PPAR, Toll-like receptor, and MTOR signaling pathways. WGCNA identified 3794 hub genes, including the CEACAM1 gene. Further Western Blot experiments indicate that in OSCC cells, the CEACAM1 gene has a negative regulatory effect on the PPAR signaling pathway, and changes in its expression levels affect the upregulation or downregulation of key molecules PPAR, ILK, and PDK1. Furthermore, the overexpression of the CEACAM1 gene can promote the expression of autophagy-related molecules such as PINK1, Parkin, LC3I, LC3II, and mitochondrial fusion-related proteins OPA1, MFN2, as well as mitochondrial biogenesis-related proteins NRF1, TFAM in OSCC cells. The overexpression of the CEACAM1 gene inhibits the expression of mitochondrial fission-related proteins and promotes the expression of apoptosis-related proteins.

CEACAM1 regulates the PPAR signaling pathway key molecules, affecting OSCC cell autophagy, mitochondrial balance, and apoptosis.