Functional exploration of PRC2 component proteins as potential prognostic markers in oral cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K10146
• 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: Sapporo Medical University
• Principal Investigator: Tange Shoichiro 札幌医科大学, 医学部, 助教 (40571211)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 口腔がん / 腫瘍マーカー / ヒストン修飾

Outline of Final Research Achievements

This study targets proteins without enzymatic activity among the Polycomb repressive complex (PRC) that contribute to transcriptional repression of target genes. Analysis of expression information on oral cancer in TCGA, a database of clinical specimens, showed that for one of the genes in this study, the recurrence-free survival of the high-expression group was significantly longer than that of the low-expression group. We performed knockdown experiments of this gene in oral cancer cell lines and analyzed the transcriptome information. The results showed that knockdown of the gene increased the expression level of a group of genes that contribute to epithelial-mesenchymal transition, one of the signs of tumor malignancy, which correlates with increased motility and acquisition of drug resistance.

Free Research Field

ゲノム医科学

Academic Significance and Societal Importance of the Research Achievements

遺伝子の転写抑制に寄与するPolycomb蛋白質複合体は、発がんや腫瘍の悪性化に寄与するという趣旨の報告が多くなされてきている。しかしながら本研究では、従来の報告とは逆に腫瘍の悪性化を阻害する形での関与を示唆する結果が得られた。この知見は、PRC2阻害薬等、将来的に薬剤を臨床的に導入する際の患者の投与適合性の是非を判断するための指標という形で社会に貢献をしうる可能性がある。