Expression mechanism of glycosyltransferase a4GnT that suppresses differentiated gastric cancer.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09075
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Shinshu University
• Principal Investigator: Kato Masayoshi 信州大学, 学術研究院医学系, 助教 (70402104)
• Co-Investigator(Kenkyū-buntansha): 中山 淳 信州大学, 学術研究院医学系, 教授 (10221459)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胃がん / A4GNT / αGlcNAc / 遺伝子発現制御

Outline of Final Research Achievements

Around the CAAT-box present in the promoter of the A4GNT gene, which suppresses cancer, was essential for this gene expression. We confirmed that one transcription factor (unpublished) binds there, however, when we suppressed the expression of the transcription factor by RNAi method and analyzed it by quantitative PCR, we found that the expression of the A4GNT gene was increased. Immunohistochemical analysis of the submucosa of the pyloric region of the human stomach revealed that the expression of the transcription factor is suppressed at the site where A4GNT is expressed, and its expression is promoted at the site where A4GNT expression is lost due to cancerization. These findings suggest that the transcription factor negatively regulates the A4GNT gene.

Free Research Field

医化学

Academic Significance and Societal Importance of the Research Achievements

この度同定したA4GNT遺伝子のプロモータに結合する転写因子は、A4GNT遺伝子発現を負に制御する可能性があるものであった。このことを胃癌の予防や治癒の観点で考えると、この転写因子を胃幽門部など特異的に局所的に発現抑制させることが発癌抑制につながる可能性は考えられる。しかしながら本研究の成果から現時点でその可能性について是非を問うには情報が不十分である。また、この転写因子でA4GNT遺伝子発現を解釈するならば、胃幽門部におけるその発現制御や機能制御についてより深く掘り下げた解析が要求される。