Investigation of the cancer-resistance mechanisms in the longest-lived rodent, the naked mole-rat.

• Project/Area Number: 21H02392
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Kumamoto University
• Principal Investigator: Miura Kyoko 熊本大学, 大学院生命科学研究部(医), 教授 (80583062)
• Co-Investigator(Kenkyū-buntansha): 坊農 秀雅 広島大学, 統合生命科学研究科(理), 教授 (20364789) ; 坂井 祐介 国立感染症研究所, 感染病理部, 主任研究官 (60615722)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2023: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000); Fiscal Year 2022: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2021: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: ハダカデバネズミ / Naked mole-rat

Outline of Research at the Start

ハダカデバネズミ（デバ）は、マウスと同等の大きさながら最大寿命が約37年の最長寿齧歯類であり、強い発がん耐性をもつ。本研究では、デバ種特異的な発がん誘導への組織応答を詳細に解析することで、本種特有の発がん耐性機構の全容解明に迫る。将来的には、本研究で解明した機構・制御遺伝子を元に、ヒトにおける新たな観点からの発がん予防/治療方法の開発が期待される。

Outline of Final Research Achievements

We showed that the naked mole-rat (NMR) exhibits significantly attenuated inflammatory responses that may play a role in suppressing cancer promotion and various age-related diseases in this species. One possible mechanism is the species-specific loss of the ability to induce necroptosis and a death-inducing mechanism in senescent cells. On the other hand, when cells were transformed by transducing oncogenes in the NMR body, tumors were formed. This suggests that there may be NMR-specific defense mechanisms that suppress or eliminate abnormal cell proliferation in the body before reaching transformation.

Academic Significance and Societal Importance of the Research Achievements

本研究が進展することで、ヒトを含む哺乳類における発がんおよびそのメカニズムの理解、また革新的な発がん予防方法につながることが期待される。