[의학신문·일간보사=이승덕 기자]A research team at the National Cancer Center has found a clue to developing a new treatment method and treatment for hepatitis C virus, which is highly likely to develop into liver cancer.
National Cancer Center: Prof. Kim Jong-heon (Senior Researcher, Cancer Molecular Biology Research Department), Researcher Seo Yuna (Cancer Molecular Biology Research Department), Professor Park Jong-bae (Director of Industry-University Cooperation, International Cancer Graduate University, National Cancer Center), Korea Research Institute of Bioscience and Biotechnology, Professor Cho Seong-chan (Senior Researcher) A joint research team announced that it had identified the key mechanism of virus proliferation in hepatitis C.
In addition, by discovering ‘Rigosertip’ as an antiviral drug candidate, we found a new way to inhibit the proliferation of hepatitis C virus.
This study related to the identification of the virus propagation mechanism of hepatitis C is an influential achievement as the discovery of hepatitis C virus won the Nobel Prize in 2020, and this study is particularly noteworthy as it is also related to microRNA (miRNA).
However, this study is related to microRNA, not mRNA, which is widely known as a vaccine to prevent COVID-19. In general, microRNAs, which are small RNA fragments with 21 to 23 sequences, have significantly different functions from existing RNAs and play a role in regulating protein expression by binding to mRNA.
However, a microRNA called microRNA-122 (miR-122), which is expressed only in the liver, has a different function. miR-122 is a 22-sequence microRNA that is expressed only in the liver. It binds to the 5′ (5 prime) end of hepatitis C virus RNA to stabilize viral RNA and amplify protein expression to help the virus propagate. give.
That is, the hepatitis C virus uses miR-122 present in human liver very skillfully for virus propagation.
Specifically, the research team identified the upper signaling pathway PLK1 (polo-like protein kinase 1)-ELAVL1/HuR (human antigen R) mechanism that regulates miR-122, which is key to viral growth, and identified ‘Rigoser’ as an antiviral drug candidate. Found a tip.
‘Rigosertip’ suppresses the proliferation of hepatitis C virus by inhibiting the kinase function of intracellular PLK1 and finally inhibiting the PLK1 sub-signaling process (ELAVL1/HuR-miR-122). The efficacy was confirmed through liver cancer cell lines and animal experiments. Rigosertip is currently undergoing phase 3 clinical trials as an anti-cancer drug candidate.
Professor Kim Jong-heon, the main corresponding author of the research paper, said, “‘Rigosertip,’ a new drug candidate discovered in relation to miR-122, will become a new therapeutic candidate for inhibiting the proliferation of hepatitis C virus, which is closely related to liver cancer in the future. “Rigosertip will be an alternative to overcome RNA virus mutation resistance, which is the Achilles’ heel of the blockbuster new drug ‘Sofosbuvir’ previously developed by Gilead Sciences,” he said.
The research team has currently completed a patent application for a luminescent sensor system that can sensitively detect the proliferation of hepatitis C virus and the regulation of microRNA-122 at the same time, and additional research for basic research, new drug development and discovery is also underway.
Meanwhile, the results of this research were published as a thesis in the latest issue of the Proceedings of the National Academy of Sciences of the United States of America (PNAS, IF 12.779), a world-renowned international academic journal, and are part of the National Cancer Center’s public interest cancer research project, the National Research Foundation of Korea’s mid-level researcher support project, and the Korea Research Institute of Bioscience and Biotechnology’s research project. done with support