Elucidating the mechanism for induction of senescence-associated secretory phenotype by Epstein-Barr virus

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H04343
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kanazawa University
• Principal Investigator: WAKISAKA NAOHIRO 金沢大学, 医学系, 准教授 (70377414)
• Co-Investigator(Kenkyū-buntansha): 吉崎 智一 金沢大学, 医学系, 教授 (70262582) ; 近藤 悟 金沢大学, 附属病院, 講師 (70436822)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 細胞老化 / Epstein-Barrウイルス / ヒト乳頭腫ウイルス / ミトコンドリア / 転移

Outline of Final Research Achievements

In the current study, we cannot find any correlated biological background between senescence-associated secretory phenotype (SASP), and cancerization and metastatic potential in both nasopharyngeal carcinoma (NPC) and oropharyngeal carcinoma (OPC). In both carcinomas, especially in NPC, mitochondrial DNA mutations were strongly correlated with metastatic potential of NPCs. We found many mitochondrial DNA mutations were due to the effect ofcytidine deaminases (CDAs) in NPC. On the other hands, the mutations were caused both by CDAs and reactive oxigen species in OPCs.
For the above-mentioned result, the existence of the phenomenon that metastasis was promoted by the mutatiions of the mitochondrial DNA was suggested. And an elucidation of the mechanisms to relate metastasis to mitochondrial DNA mutations is needed in the future study.

Free Research Field

頭頸部外科

Academic Significance and Societal Importance of the Research Achievements

本研究は当初、SASPと発癌・転移の関連性を解明すべく開始したが、その関連性は証明されなかった。SASPの誘因としてミトコンドリアDNAの変異が指摘されているが、本研究では、次世代シークエンサーによる解析の結果、SASP現象よりもミトコンドリアDNAの変異が転移促進の主要因の一つとして抽出された。
頭頸部癌、特にウイルス関連癌の転移機構研究の方向性として、ミトコンドリアDNA変異による転移機構の解明が今後の研究課題として示された意義は大きい。