ArticleHuman molecular genetics2024
An endogenous retrovirus regulates tumor-specific expression of the immune transcriptional regulator SP140.
Article in Human molecular genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Activation of transposable elements is linked to a region- and cell type-specific interferon response in Parkinson's disease.Science advances · 2026Article
- Machine learning-based identification of histone deacetylase-associated prognostic factors and prognostic modeling for low-grade glioma.Discover oncology · 2024Article
- From Junk DNA to Genomic Treasure: Impacts of Transposable Element DNA, RNA, and Protein in Mammalian Development and Disease.Wiley interdisciplinary reviews. RNAReview
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Authors and funding
3 authors.
Funding
Abstract
Speckled Protein 140 (SP140) is a chromatin reader with critical roles regulating immune cell transcriptional programs, and SP140 splice variants are associated with immune diseases including Crohn's disease, multiple sclerosis, and chronic lymphocytic leukemia. SP140 expression is currently thought to be restricted to immune cells. However, by analyzing human transcriptomic datasets from a wide range of normal and cancer cell types, we found recurrent cancer-specific expression of SP140, driven by an alternative intronic promoter derived from an intronic endogenous retrovirus (ERV). The ERV belongs to the primate-specific LTR8B family and is regulated by oncogenic mitogen-activated protein kinase (MAPK) signaling. The ERV drives expression of multiple cancer-specific isoforms, including a nearly full-length isoform that retains all the functional domains of the full-length canonical isoform and is also localized within the nucleus, consistent with a role in chromatin regulation. In a fibrosarcoma cell line, silencing the cancer-specific ERV promoter of SP140 resulted in increased sensitivity to interferon-mediated cytotoxicity and dysregulation of multiple genes. Our findings implicate aberrant ERV-mediated SP140 expression as a novel mechanism contributing to immune gene dysregulation in a wide range of cancer cells.
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