Elucidation of the mechanism of treatment resistance in oral cancer via crosstalk between metabolism and epigenome by oral microbiome.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K10118
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Kumamoto University
• Principal Investigator: Hirosue Akiyuki 熊本大学, 大学院生命科学研究部(医), 特定研究員 (00638182)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 口腔癌 / 口腔細菌叢 / 酪酸 / エピゲノム / 代謝 / 治療抵抗性

Outline of Final Research Achievements

The morbidity of oral cancer is increasing and the presence of therapeutic resistant cancer cells is a major factor contributing to decreased survival. Human microbiota affect the metabolism and epigenome of the host and are associated with pathological changes in disease. In this study, to elucidate the mechanisms of therapeutic resistance in oral cancer, we focused on butyrate produced by oral microbiome to capture metabolic and epigenomic changes in oral cancer cells. Butyrate decreased the expression of genes involved in the cell cycle of oral cancer cells through epigenetic changes and suppresses cell proliferation. It was also found to affect energy metabolism and act in a cancer-suppressive manner. These results suggest that modulating butyrate of an oral bacterial metabolite may be a novel therapeutic strategy for oral cancer.

Free Research Field

口腔癌

Academic Significance and Societal Importance of the Research Achievements

口腔癌の治療抵抗性に関して口腔細菌が産生する酪酸に着目した研究はほとんどない。そのため癌の治療抵抗性に関して、口腔細菌が産生する代謝物による代謝とエピゲノムのクロストークを介したがんの細胞制御を明らかにする本研究は口腔癌の新規の治療戦略となり得る可能性もあり学術的意義が大きい。また本研究は口腔癌やそれ以外のがん研究の発展に寄与するだけでなく、幅広い生命現象へ関与しているエピゲノムの制御機構や代謝システムを解明することで、様々な疾患の診断・治療に貢献出来る可能性もあり社会的意義も大きい。