Identification and clinical implications of endogenous retrovirus elements suppressed by SETDB1 in hepatocellular carcinoma
An inverse relationship between retroelements including human endogenous retrovirus (HERV) elements and <i>SETDB1</i> expression was observed in human hepatocellular carcinoma (HCC) by The Cancer Genome Atlas data analysis. We identified four HERV elements downregulated by SETDB1-dependent H3K9me3 in HCC cells, with low expression levels of these HERV elements correlating with poor prognosis in patients with HCC. <i>SETDB1</i> depletion resulted in upregulation of various interferon-stimulated genes associated with viral mimicry in HCC cells. These findings suggest that the four SETDB1-regulated HERVs could serve as prognostic markers and potential therapeutic targets for HCC.
Authors
- Keiichi Akahoshi (ORCID: https://orcid.org/0000-0003-3792-5659)
- Yoshimitsu Akiyama (ORCID: https://orcid.org/0000-0003-2329-8041)
- Shuichi Watanabe
- Keita Kodera
- Megumi Hatano
- Shu Tsukihara (ORCID: https://orcid.org/0000-0003-2537-719X)
- Kentaro Umemura (ORCID: https://orcid.org/0000-0003-1259-5438)
- Tomohiko Taniai (ORCID: https://orcid.org/0000-0001-8911-5530)
- Koichiro Haruki (ORCID: https://orcid.org/0000-0002-1686-3228)
- Atsushi Kamachi (ORCID: https://orcid.org/0000-0002-4012-0459)
- Yoshiaki Tanji (ORCID: https://orcid.org/0009-0004-6585-3220)
- Toru Ikegami (ORCID: https://orcid.org/0000-0001-5792-5045)
- Kenei Furukawa
- Shinji Tanaka (ORCID: https://orcid.org/0000-0002-7718-3453)
- Hiroaki Ono (ORCID: https://orcid.org/0000-0001-9230-5714)
- Koya Yasukawa (ORCID: https://orcid.org/0000-0002-3643-0921)
- Yosuke Igarashi (ORCID: https://orcid.org/0000-0003-1998-8074)
- Shu Shimada (ORCID: https://orcid.org/0000-0002-4962-0636)
- Minoru Tanabe (ORCID: https://orcid.org/0000-0003-4875-1471)
- Atsushi Nara (ORCID: https://orcid.org/0000-0001-9233-8911)
- Kohei Okazaki
- Masahiro Yamane (ORCID: https://orcid.org/0009-0004-6251-8654)
Institutions
- Jikei University School of Medicine (JP)
- Tokyo Medical and Dental University (JP)
- Shinshu University (JP)
Publication Details
- Journal
- JHEP Reports
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1016/j.jhepr.2024.101307
- Citations
- 7
- Primary Topic
- Chromosomal and Genetic Variations
- Type
- article
- Field-Weighted Citation Impact
- 4.20
Funders
- Japan Agency for Medical Research and Development
- Princess Takamatsu Cancer Research Fund
- Japan Society for the Promotion of Science