APOBEC-mediated gene mutagenesis and mechanism of CIN progression induced by infection

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16792
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Kanazawa University
• Principal Investigator: IIZUKA TAKASHI 金沢大学, 医学系, 助教 (90748617)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 子宮頸部異形成 / APOBEC / ヒトパピローマウイルス / 突然変異 / 自然免疫

Outline of Final Research Achievements

Previous studies have suggested association between cervical dysplasia and APOBEC3 expression. In the present study, cervical infection and APOBEC3 expression were examined using cultured cells. The expression of APOBEC3A was found to be up-regulated in studies using interferon and toll-like receptor 9 ligands as innate immune mechanisms. This expression was suggested to be synergistic with the ligands of interferon and tor-like receptor 9.
In addition, the action of these molecules may result in hype- mutations of HPV-DNA in cells.

Free Research Field

産科婦人科

Academic Significance and Societal Importance of the Research Achievements

子宮頸部上皮における感染・炎症においてAPOBEC3Aという抗ウイルス作用を示す自然免疫機構の酵素が関係していることが示唆された。APPBEC3Aは子宮頸部異形成細胞においてHPVウイルスゲノムの突然変異および宿主DNAへの組み込みに関係している可能性があり、この酵素の有無が子宮頸部異形成の進行にどのような影響を与えるのかを今後検討する必要があり、新たな治療法の開発やマーカーに発見に至る可能性がある。