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Satellite repeat RNA expression in epithelial ovarian cancer associates with a tumor-immunosuppressive phenotype
Open accessAbstract
Aberrant expression of viral-like repeat elements is a common feature of epithelial cancers, and the substantial diversity of repeat species provides a distinct view of the cancer transcriptome. Repeatome profiling across ovarian, pancreatic, and colorectal cell lines identifies distinct clustering independent of tissue origin that is seen with coding gene analysis. Deeper analysis of ovarian cancer cell lines demonstrated that human satellite II (HSATII) satellite repeat expression was highly associated with epithelial-mesenchymal transition (EMT) and anticorrelated with IFN-response genes indicative of a more aggressive phenotype. SATII expression - and its correlation with EMT and anticorrelation with IFN-response genes - was also found in ovarian cancer RNA-Seq data and was associated with significantly shorter survival in a second independent cohort of patients with ovarian cancer. Repeat RNAs were enriched in tumor-derived extracellular vesicles capable of stimulating monocyte-derived macrophages, demonstrating a mechanism that alters the tumor microenvironment with these viral-like sequences. Targeting of HSATII with antisense locked nucleic acids stimulated IFN response and induced MHC I expression in ovarian cancer cell lines, highlighting a potential strategy of modulating the repeatome to reestablish antitumor cell immune surveillance.
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Noncoding hSATII RNA is highly expressed in most cancer cells and tissues.
“Previous reports demonstrated that noncoding hSATII RNA is highly expressed in most cancer cells and tissues (27–32).”
From Chromatin conformational changes at human satellite II contribute to the senescence phenotype in the tumor microenvironment (2023) · cites this paper as [31]
The Results section (page unavailable) says HSATII was previously found enriched across epithelial cancers and reports high expression in some ovarian-cancer cell lines and tumors. It does not establish high expression in most cancer cells and tissues; the ovarian samples are explicitly divided into HSATII-high and HSATII-low groups. (LLM, conf=0.86)
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Metadata
- Authors
- Porter, R. L., Sun, S., Flores, M. N., Berzolla, E., You, E., Phillips, I. E., KC, N., Desai, N., Tai, E. C., Szabolcs, A., Lang, E. R., Pankaj, A., Raabe, M. J., Thapar, V., Xu, K. H., Nieman, L. T., Rabe, D. C., Kolin, D. L., Stover, E. H., Pepin, D., Stott, S. L., Deshpande, V., Liu, J. F., Solovyov, A., Matulonis, U. A., Greenbaum, B. D., & Ting, D. T.
- Affiliations
- Harvard University (US)
- Memorial Sloan Kettering Cancer Center (US)
- Brigham and Women's Hospital (US)
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Ting, David T.
- ORCID
- Porter, Rebecca L.
- Sun, Siyu
- Flores, Micayla N.
- Berzolla, Emily
- You, Eunae
- Phillips, Ildiko E.
- Desai, Niyati
- Lang, Evan R.
- Pankaj, Amaya
- Raabe, Michael J.
- Thapar, Vishal
- Xu, Katherine H.
- Nieman, Linda T.
- Rabe, Daniel C.
- Kolin, David L.
- Stover, Elizabeth H.
- Pepin, David
- Stott, Shannon L.
- Deshpande, Vikram
- Liu, Joyce F.
- Solovyov, Alexander
- Matulonis, Ursula A.
- Greenbaum, Benjamin D.
- Ting, David T.
- Venue
- Journal of Clinical Investigation
- Published
- 2022-08-15
- Volume
- 132
- Issue
- 16
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC9374379
- OpenAlex
- W4282980840
- Cited by
- 24
- References
- 53
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 9 · 2022: 3
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Investigation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Cancer Institute (R01CA240924, U01CA228963)
- U.S. Department of Defense (OC180106)
- Robert L. Fine Cancer Research Foundation (Robert L. Fine Cancer Research Foundation)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- epithelial ovarian cancer, repeatome, epithelial-mesenchymal transition, interferon response, tumor immunosuppression, extracellular vesicles, macrophage polarization, tumor microenvironment, patient survival, MHC class I expression, tumor surveillance
- MeSH terms
- Carcinoma, Ovarian Epithelial, Female, Humans, Ovarian Neoplasms, Phenotype, RNA, Gene Expression Regulation, Neoplastic, RNA, Satellite, Cell Line, Tumor, Epithelial-Mesenchymal Transition, Tumor Microenvironment
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