[P1-2-40] Functional analysis of EGR-1 as a tumor suppressor gene in oral squamous cell carcinoma
Keywords:口腔癌、EGR-1、癌抑制遺伝子
[Background and Purpose]Oral cancer is estimated to affect about 8000 people each year in Japan, accounting for about 1% of all cancers. Although squamous cell carcinoma accounts for 90% of the cases, the mechanisms of development, invasion, and metastasis are still unknown. In addition, surgical resection is performed in many cases, but the postoperative deterioration of oral functions and changes in facial appearance are significant, and early detection and less invasive treatment are expected. In this study, we performed functional analysis of the early response gene EGR-1, a transcription factor with Zinc-finger, in oral cancer and examined its potential as a tumor suppressor gene.[Methods and Results]In TCGA data set, EGR-1 expression was shown to be significantly lower in tumor tissues than in normal tissues. Functional inhibition of HSC3M3, a human oral squamous cell carcinoma cell line, using si-RNA resulted in increased cell proliferative capacity by WST-8 assay, invasive capacity by invasion assay, and migratory capacity by wound healing assay. Gene analysis using qRT-PCR showed significant increases in cell cycle markers, MMPs, and EMT markers. On the other hand, strong expression of function using plasmid showed a significant decrease in cell proliferation, invasive and migratory ability, and a significant decrease in each marker at the gene level. In addition, western blot analysis showed significant changes in the expression of cell cycle regulators. In addition, immunohistochemistry of 63 cases showed a significant decrease in the percentage of area occupied by EGR-1 expression in tumor foci compared to normal tissue.[Discussion]This study suggests that EGR-1 functions as a tumor suppressor gene in oral cancer. We plan to conduct more detailed pathway analysis and to study the relationship with metastasis and the microenvironment based on animal experiments in the future.