Pericentromeric satellite repeat expansions through RNA-derived DNA intermediates in cancer
Open accessAbstract
Significance: Unique among the large number of noncoding RNA species, the pericentromeric human satellite II (HSATII) repeat is massively expressed in a broad set of epithelial cancers but is nearly undetectable in normal tissues. Here, we show that deregulation of HSATII expression is tightly linked to growth under nonadherent conditions, and we uncover an unexpected mechanism by which HSATII RNA-derived DNA (rdDNA) leads to progressive elongation of pericentromeric regions in tumors. The remarkable specificity of HSATII overexpression in cancers, together with the consequences of targeting its RT, points to a potential novel vulnerability of cancer cells.
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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 [28]
Cites
Counter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096 · cited 1× · see citing works
“The mechanism underlying HSATII satellite repeat expansion in cancer remains to be defined, but it may involve an RT/ reintegration phenomenon analogous to the phenomenon described for other major repetitive elements, such as LINE-1 (24) and telomeres (25, 26).”
BackgroundDai, L., Huang, Q., & Boeke, J. D. (2011) · BMC Biochemistry · doi:10.1186/1471-2091-12-18 · Cited by 131 · see citing works
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Ishak, C. A., Marshall, A. E., Passos, D. T., White, C. R., Kim, S. J., Cecchini, M. J., Ferwati, S., MacDonald, W. A., Howlett, C. J., Welch, I. D., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.10.021 · Cited by 167 · see citing works
Miyata, K., Imai, Y., Hori, S., Nishio, M., Loo, T. M., Okada, R., Yang, L., Nakadai, T., Maruyama, R., Fujii, R., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2025647118 · Cited by 74 · see citing works
Sequence-Specific Sensing of Nucleic Acids
Vabret, N., Bhardwaj, N., & Greenbaum, B. D. (2017) · Trends in Immunology · doi:10.1016/j.it.2016.10.006 · Cited by 45 · see citing works
Nogalski, M. T., & Shenk, T. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2017734117 · Cited by 25 · see citing works
Miyata, K., Zhou, X., Nishio, M., Hanyu, A., Chiba, M., Kawasaki, H., Osako, T., Takeuchi, K., Ohno, S., Ueno, T., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2305046120 · Cited by 13 · see citing works
Dumetier, B., Sauter, C., Hajmirza, A., Pernon, B., Aucagne, R., Fournier, C., Row, C., Guidez, F., Rossi, C., Lepage, C., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10123101 · Cited by 9 · see citing works
Pericentromeric repetitive ncRNA regulates chromatin interaction and inflammatory gene expression
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- Authors
- Bersani, F., Lee, E., Kharchenko, P. V., Xu, A. W., Liu, M., Xega, K., MacKenzie, O. C., Brannigan, B. W., Wittner, B. S., Jung, H., Ramaswamy, S., Park, P. J., Maheswaran, S., Ting, D. T., & Haber, D. A.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Howard Hughes Medical Institute (US)
- Samsung Medical Center (KR)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-11-02
- Volume
- 112
- Issue
- 49
- Pages
- 15148-15153
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4679016
- OpenAlex
- W2255688436
- Cited by
- 181
- References
- 2
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 17 · 2023: 13 · 2022: 31 · 2021: 30 · 2020: 19 · 2019: 19 · 2018: 13 · 2017: 10 · 2016: 6 · 2015: 2
- FWCI
- 12.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Funders
- Howard Hughes Medical Institute (Investigator)
- U.S. Department of Defense (W81XWH-13-1-0237)
- HHS | NIH | National Cancer Institute (R01CA129933, K12CA087723-11A1)
- National Foundation for Cancer Research (Investigator)
- Burroughs Wellcome Fund (1010968.01)
- Susan G. Komen for the Cure (KG09042)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- RNA-DNA hybrids, repeat expansion, copy number gain, aberrant transcription, colon cancer, tumor xenografts, reverse transcriptase inhibition, overall survival
- MeSH terms
- Centromere, DNA, Satellite, Humans, Neoplasms, Nucleic Acid Hybridization, Repetitive Sequences, Nucleic Acid, RNA, Colorectal Neoplasms
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