2023 Fiscal Year Final Research Report
Molecular function of RNA binding protein of endogenous retroviruses
Project/Area Number |
21K05930
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 42020:Veterinary medical science-related
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Research Institution | Jichi Medical University |
Principal Investigator |
Nakaya Yuki 自治医科大学, 医学部, 講師 (00713562)
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Keywords | 内在性レトロウイルス / HML-2 / 肝臓 / 組織特異的発現 / スプライシング / 核外輸送タンパク / がん / シグナル伝達 |
Outline of Final Research Achievements |
In this study, the investigator analyzed the molecular function of a newly identified gene which was derived from a human endogenous retrovirus (HERV). The HERV possessed a gene, HML-2-X, which is generated by an alternative splicing of its envelope gene. HML-2-X was preferentially expressed in the normal liver tissues and primary human hepatocytes, PXB-cells, that were derived from chimeric mice with human hepatocytes. On the other hand, the expression level of HML-2-X was significantly decreased in the liver cancer tissues and hepatocellular carcinoma cell lines (HCCs). Oncogenic signaling pathways such as WNT/β-catenin signaling were inactivated in HCCs stably transfected with HML-2-X, which resulted in the attenuation of cellular growth kinetics and migration activity. Here the investigator demonstrated a novel function of HERV that HML-2-X potentially suppresses the development of liver cancer by modulating the cellular signaling pathways.
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Free Research Field |
ウイルス学
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Academic Significance and Societal Importance of the Research Achievements |
ヒトゲノムには多数のHERVが組込まれているが、ほとんどのHERVの役割が明らかにされておらず、その解明が望まれている。また、近年、肝炎ウイルス感染に起因する肝がんは減少傾向にあるものの、肝炎ウイルス感染を伴わない肝がんが増加傾向にある。そのため、これらの予防と治療へ向けた、肝細胞のがん化機構に関する基礎研究の重要性が大きくなりつつある。本研究成果は、HERV由来遺伝子による肝がん抑制機構という、ウイルス学や進化学など基礎学術分野において、非常に興味深い新たな分子機構を提唱するものである。加えて、肝がんの予防法や治療法の発展に向け、新たな洞察を与えるものであり、臨床医学への応用が期待される。
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