Molecular mechanisms of HBV replication and liver cancer malignant progression by a novel lncRNA ELIT-1

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07569
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Sakai Satoshi 浜松医科大学, 医学部, 助教 (50566081)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: lncRNA / がん遺伝子 / がん抑制遺伝子 / シグナル伝達

Outline of Final Research Achievements

The aim of our study was to analyse the function of lncRNA ELIT-1 in HBV replication. However, knockdown of ELIT-1 or compounds obtained by screening for inhibitors of ELIT-1 expression did not affect in a significant reduction of hepatitis B virus.
On the other hand, we focused on lincNMR as another lncRNA whose expression is upregulated during HBV replication. We reported that lincNMR is an oncogene that positively regulates APOBEC3B, which is involved in DNA mutations (Carcinogenesis, 2023). Furthermore, we reported that LINC00173, a reported tumor suppressor, bound to SNAIL and inhibited the down-regulation of the tumor suppressor FHIT by SNAIL (Int. J. Mol. Sci., 2023).

Free Research Field

シグナル伝達

Academic Significance and Societal Importance of the Research Achievements

ELIT-1の発現阻害剤のスクリーニングから得た化合物はB型肝炎ウイルス量の顕著な低下を示さなかった。しかし、ELIT-1は上皮間葉転換（EMT）を促進する機能を持っている(Sakai et al., Cancer Res., 2019)。本成果で得られた化合物は、がんの転移阻害剤、肝線維化阻害剤として有用となる可能性がある。また、HBV複製時に発現上昇したlincNMRが、がんの悪性化に関わることも発見できた。今後lincNMRの発現阻害剤を探索することで、HBVを起点とする肝がんの進展阻害剤を見出すことが出来る可能性がある。