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Human endogenous retrovirus-K (HERV-K) is the most recently integrated retrovirus in the human genome, with implications for multiple disorders, including cancer. Although typically transcriptionally silenced in normal adult cells, dysregulation of HERV-K (HML-2) elements has been observed in cancer, including breast, germ cell tumors, pancreatic, melanoma, and brain cancer. While multiple methods of carcinogenesis have been proposed, here we discuss the role of HERV-K (HML-2) in the promotion and maintenance of the stem-cell in cancer. Aberrant expression of HERV-K has been shown to promote expression of stem cell markers and promote dedifferentiation. In this review, we discuss HERV-K (HML-2) as a potential therapeutic target based on evidence that some tumors depend on the expression of its proteins for survival.
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http://dx.doi.org/10.3390/v14092019 | DOI Listing |
J Immunother Cancer
August 2025
Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, Université Claude Bernard Lyon 1, Inserm 1052, CNRS 5286, Lyon, France
Background: Ovarian cancer represents the most lethal gynecological cancer with poor response to checkpoint inhibitors. Human endogenous retroviruses (HERVs) are aberrantly expressed by tumor cells and may represent a source of shared T-cell epitopes for cancer immunotherapy regardless of the tumor mutational burden.
Methods: A transcriptomic analysis based on RNA sequencing was developed to quantify the expression of HERV-K sequences containing the selected epitopes.
bioRxiv
July 2025
Myles H. Thaler Center for AIDS and Human Retrovirus Research, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
Human Endogenous Retroviruses K (HERV-K) of the HML-2 subgroup are the most recently integrated and biologically active retroviral elements within the human genome. The HERV-K Rec protein, a functional homolog of HIV Rev and HTLV Rex, is necessary for the nuclear export of viral mRNAs with retained introns. However, the diversity of Rec proteins encoded in the human genome and their functional capacities have remained largely unexplored.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
July 2025
Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
The human endogenous retrovirus K (HERV-K) is a retrovirus that got assimilated into the human genome in ancient times and has been inherited in our germline ever since. It enters cells using a class-I spike protein (Env) that mediates receptor recognition and membrane fusion. On top of having a biological role during development, HERV-K is activated in amyotrophic lateral sclerosis, various cancers, and other pathological conditions.
View Article and Find Full Text PDFInfect Agent Cancer
June 2025
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Objective: Bladder cancer (BCa) has become a growing concern worldwide, highlighting the importance of early detection and new treatment methods. Recent studies have shown that viruses from the HERV family play a significant role in the development of various cancers and can act as early diagnostic biomarkers. Although hypomethylation of HERV-K has been proven in bladder cancer, no studies have yet explored the role of HERV-K oncogenes such as env, gag, np9, and rec.
View Article and Find Full Text PDFMob DNA
May 2025
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Human endogenous retroviruses (HERVs) occupy 8% of the human genome. Although most HERV integrations are severely degenerated by mutations, the most recently integrated proviruses, such as members of the HERV-K HML-2 subfamily, partially retain regulatory and protein-coding capacity. The precise number of HML-2 proviral copies in the modern human population is constantly changing in literature, as new integrations are being uncovered.
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