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Long noncoding RNAs and the genetics of cancer
Open accessAbstract
Cancer is a disease of aberrant gene expression. While the genetic causes of cancer have been intensively studied, it is becoming evident that a large proportion of cancer susceptibility cannot be attributed to variation in protein-coding sequences. This is highlighted by genome-wide association studies in cancer that reveal that more than 80% of cancer-associated SNPs occur in noncoding regions of the genome. In this review, we posit that a significant fraction of the genetic aetiology of cancer is exacted by noncoding regulatory sequences, particularly by long noncoding RNAs (lncRNAs). Recent studies indicate that several cancer risk loci are transcribed into lncRNAs and these transcripts play key roles in tumorigenesis. We discuss the epigenetic and other mechanisms through which lncRNAs function and how they contribute to each stage of cancer progression, understanding of which will be crucial for realising new opportunities in cancer diagnosis and treatment. Long noncoding RNAs play important roles in almost every aspect of cell biology from nuclear organisation and epigenetic regulation to post-transcriptional regulation and splicing, and we link these processes to the hallmarks and genetics of cancer. Finally, we highlight recent progress and future potential in the application of lncRNAs as therapeutic targets and diagnostic markers.
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Cites
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
Long non-coding RNAs: insights into functions
Mercer, T. R., Dinger, M. E., & Mattick, J. S. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2521 · Cited by 5,654
Self-citationKhalil, A. M., Guttman, M., Huarte, M., Garber, M., Raj, A., Rivea Morales, D., Thomas, K., Presser, A., Bernstein, B. E., van Oudenaarden, A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904715106 · Cited by 2,872
Specific expression of long noncoding RNAs in the mouse brain
Mercer, T. R., Dinger, M. E., Sunkin, S. M., Mehler, M. F., & Mattick, J. S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706729105 · Cited by 1,103
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Cited by
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Long non-coding RNAs and complex diseases: from experimental results to computational models
Chen, X., Yan, C. C., Zhang, X., & You, Z.-H. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw060 · Cited by 567
Discovery of common and rare genetic risk variants for colorectal cancer
Huyghe, J. R., Bien, S. A., Harrison, T. A., Kang, H. M., Chen, S., Schmit, S. L., Conti, D. V., Qu, C., Jeon, J., Edlund, C. K., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0286-6 · Cited by 544
Potential of long non‐coding RNAs in cancer patients: From biomarkers to therapeutic targets
Chandra Gupta, S., & Nandan Tripathi, Y. (2017) · International Journal of Cancer · doi:10.1002/ijc.30546 · Cited by 527
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Metadata
- Authors
- Cheetham, S. W., Gruhl, F., Mattick, J. S., & Dinger, M. E.
- Venue
- British Journal of Cancer
- Published
- 2013-05-09
- Volume
- 108
- Issue
- 12
- Pages
- 2419-2425
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- OpenAlex
- W2059191987
- Cited by
- 724
- References
- 4
- FWCI
- 23.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
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