ArticleScientific reports2021
SMARCB1 deletion in atypical teratoid rhabdoid tumors results in human endogenous retrovirus K (HML-2) expression.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- A Systematic Review of Expression and Immunogenicity of Human Endogenous Retroviral Proteins in Cancer and Discussion of Therapeutic Approaches.International journal of molecular sciences · 2022Pooled it
- Clinicopathological Characterization of Pediatric Atypical Teratoid/Rhabdoid Tumors and an HE-IHC Dual-Path Deep Learning Model for Auxiliary Diagnosis.Diagnostics (Basel, Switzerland) · 2026Article
- Immune landscape of the affected brain in Rasmussen encephalitis.Scientific reports · 2026Article
- Pediatric Spinal Atypical Teratoid Rhabdoid Tumor: Recent Advances in Biology and Management Options.Cancers · 2026Review
- SMARCB1/INI1-deficient carcinoma with yolk sac tumor-like features in the inguinal region of a young man: a case of a deceptive and emerging entity.Virchows Archiv : an international journal of pathology · 2026Article
- Expression of LTR and LINE1 transposable elements defines atypical teratoid/rhabdoid tumor subtypes.Acta neuropathologica communications · 2025Article
- Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging.Translational neurodegeneration · 2025Review
- Activation of human endogenous retroviruses by Sox proteins induces cell apoptosis via the caspase-3 pathway.Frontiers in microbiology · 2025Article
- Species-Specific Transcription Factors Associated with Long Terminal Repeat Promoters of Endogenous Retroviruses: A Comprehensive Review.Biomolecules · 2024Review
- HERVK-mediated regulation of neighboring genes: implications for breast cancer prognosis.Retrovirology · 2024Article
- A rapid and stable spontaneous reprogramming system of Spermatogonial stem cells to Pluripotent State.Cell & bioscience · 2023Article
- Does the interplay between human endogenous retrovirus K and extracellular vesicles contribute to aging?Extracellular vesicles and circulating nucleic acids · 2023Article
- Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma.The Journal of clinical investigation · 2023Article
- Epigenetic Regulation in Primary CNS Tumors: An Opportunity to Bridge Old and New WHO Classifications.Cancers · 2023Review
- Review
- HERVs and Cancer-A Comprehensive Review of the Relationship of Human Endogenous Retroviruses and Human Cancers.Biomedicines · 2023Review
- The Role of HERV-K in Cancer Stemness.Viruses · 2022Review
- Retroviral Elements in Pathophysiology and as Therapeutic Targets for Amyotrophic Lateral Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Molecular targeted therapies for pediatric atypical teratoid/rhabdoid tumors.Pediatric investigation · 2022Review
- Differential expression of an endogenous retroviral element [HERV-K(HML-6)] is associated with reduced survival in glioblastoma patients.Scientific reports · 2022Article
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Atypical Teratoid Rhabdoid Tumor (AT/RT) is a rare pediatric central nervous system cancer often characterized by deletion or mutation of SMARCB1, a tumor suppressor gene. In this study, we found that SMARCB1 regulates Human Endogenous Retrovirus K (HERV-K, subtype HML-2) expression. HML-2 is a repetitive element scattered throughout the human genome, encoding several intact viral proteins that have been associated with stem cell maintenance and tumorigenesis. We found HML-2 env expression in both the intracellular and extracellular compartments in all AT/RT cell lines (n = 4) and in 95% of AT/RT patient tissues (n = 37) evaluated. SMARCB1 knock-down in neural stem cells (NSCs) led to an upregulation of HML-2 transcription. We found that SMARCB1 binds adjacent to the HML-2 promoter, repressing its transcription via chromatin immunoprecipitation; restoration of SMARCB1 expression in AT/RT cell lines significantly downregulated HML-2 expression. Further, targeted downregulation of HML-2 transcription via CRISPR-dCas9 coupled with suppressor proteins led to cellular dispersion, decreased proliferation, and cell death in vitro. HML-2 knock-down with shRNA, siRNA, and CRISPR-dCas9 significantly decreased Ras expression as measured by qRT-PCR, suggesting that HML-2 modulates MAPK/ERK signaling in AT/RT cells. Overexpression of NRAS was sufficient to restore cellular proliferation, and MYC, a transcription factor downstream of NRAS, was bound to the HERV-K LTR significantly more in the absence of SMARCB1 expression in AT/RT cells. We show a mechanism by which these undifferentiated tumors remain pluripotent, and we demonstrate that their formation is aided by aberrant HML-2 activation, which is dependent on SMARCB1 and its interaction with MYC.
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