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Differential expression of an endogenous retroviral element [HERV-K(HML-6)] is associated with reduced survival in glioblastoma patients
Comprising approximately 8% of our genome, Human Endogenous RetroViruses (HERVs) represent a class of germline retroviral infections that are regulated through epigenetic modifications. In cancer cells, which often have epigenetic dysregulation, HERVs have been implicated as potential oncogenic driv...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046263/ https://www.ncbi.nlm.nih.gov/pubmed/35477752 http://dx.doi.org/10.1038/s41598-022-10914-5 |
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author | Shah, Ashish H. Govindarajan, Vaidya Doucet-O’Hare, Tara T. Rivas, Sarah Ampie, Leo DeMarino, Catherine Banasavadi-Siddegowda, Yeshavanth Kumar Zhang, Yong Johnson, Kory R. Almsned, Fahad Gilbert, Mark R. Heiss, John D. Nath, Avindra |
author_facet | Shah, Ashish H. Govindarajan, Vaidya Doucet-O’Hare, Tara T. Rivas, Sarah Ampie, Leo DeMarino, Catherine Banasavadi-Siddegowda, Yeshavanth Kumar Zhang, Yong Johnson, Kory R. Almsned, Fahad Gilbert, Mark R. Heiss, John D. Nath, Avindra |
author_sort | Shah, Ashish H. |
collection | PubMed |
description | Comprising approximately 8% of our genome, Human Endogenous RetroViruses (HERVs) represent a class of germline retroviral infections that are regulated through epigenetic modifications. In cancer cells, which often have epigenetic dysregulation, HERVs have been implicated as potential oncogenic drivers. However, their role in gliomas is not known. Given the link between HERV expression in cancer cell lines and the distinct epigenetic dysregulation in gliomas, we utilized a tailored bioinformatic pipeline to characterize and validate the glioma retrotranscriptome and correlate HERV expression with locus-specific epigenetic modifications. We identified robust overexpression of multiple HERVs in our cell lines, including a retroviral transcript, HML-6, at 19q13.43b in glioblastoma cells. HERV expression inversely correlated with loci-specific DNA methylation. HML-6 contains an intact open reading frame encoding a small envelope protein, ERVK3-1. Increased expression of ERVK3-1 in GBM patients is associated with a poor prognosis independent of IDH-mutational status. Our results suggest that not only is HML-6 uniquely overexpressed in highly invasive cell lines and tissue samples, but also its gene product, ERVK3-1, may be associated with reduced survival in GBM patients. These results may have implications for both the tumor biology of GBM and the role of ERVK3-1 as a potential therapeutic target. |
format | Online Article Text |
id | pubmed-9046263 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90462632022-04-29 Differential expression of an endogenous retroviral element [HERV-K(HML-6)] is associated with reduced survival in glioblastoma patients Shah, Ashish H. Govindarajan, Vaidya Doucet-O’Hare, Tara T. Rivas, Sarah Ampie, Leo DeMarino, Catherine Banasavadi-Siddegowda, Yeshavanth Kumar Zhang, Yong Johnson, Kory R. Almsned, Fahad Gilbert, Mark R. Heiss, John D. Nath, Avindra Sci Rep Article Comprising approximately 8% of our genome, Human Endogenous RetroViruses (HERVs) represent a class of germline retroviral infections that are regulated through epigenetic modifications. In cancer cells, which often have epigenetic dysregulation, HERVs have been implicated as potential oncogenic drivers. However, their role in gliomas is not known. Given the link between HERV expression in cancer cell lines and the distinct epigenetic dysregulation in gliomas, we utilized a tailored bioinformatic pipeline to characterize and validate the glioma retrotranscriptome and correlate HERV expression with locus-specific epigenetic modifications. We identified robust overexpression of multiple HERVs in our cell lines, including a retroviral transcript, HML-6, at 19q13.43b in glioblastoma cells. HERV expression inversely correlated with loci-specific DNA methylation. HML-6 contains an intact open reading frame encoding a small envelope protein, ERVK3-1. Increased expression of ERVK3-1 in GBM patients is associated with a poor prognosis independent of IDH-mutational status. Our results suggest that not only is HML-6 uniquely overexpressed in highly invasive cell lines and tissue samples, but also its gene product, ERVK3-1, may be associated with reduced survival in GBM patients. These results may have implications for both the tumor biology of GBM and the role of ERVK3-1 as a potential therapeutic target. Nature Publishing Group UK 2022-04-27 /pmc/articles/PMC9046263/ /pubmed/35477752 http://dx.doi.org/10.1038/s41598-022-10914-5 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Shah, Ashish H. Govindarajan, Vaidya Doucet-O’Hare, Tara T. Rivas, Sarah Ampie, Leo DeMarino, Catherine Banasavadi-Siddegowda, Yeshavanth Kumar Zhang, Yong Johnson, Kory R. Almsned, Fahad Gilbert, Mark R. Heiss, John D. Nath, Avindra Differential expression of an endogenous retroviral element [HERV-K(HML-6)] is associated with reduced survival in glioblastoma patients |
title | Differential expression of an endogenous retroviral element [HERV-K(HML-6)] is associated with reduced survival in glioblastoma patients |
title_full | Differential expression of an endogenous retroviral element [HERV-K(HML-6)] is associated with reduced survival in glioblastoma patients |
title_fullStr | Differential expression of an endogenous retroviral element [HERV-K(HML-6)] is associated with reduced survival in glioblastoma patients |
title_full_unstemmed | Differential expression of an endogenous retroviral element [HERV-K(HML-6)] is associated with reduced survival in glioblastoma patients |
title_short | Differential expression of an endogenous retroviral element [HERV-K(HML-6)] is associated with reduced survival in glioblastoma patients |
title_sort | differential expression of an endogenous retroviral element [herv-k(hml-6)] is associated with reduced survival in glioblastoma patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046263/ https://www.ncbi.nlm.nih.gov/pubmed/35477752 http://dx.doi.org/10.1038/s41598-022-10914-5 |
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