Long noncoding RNAs and the genetics of cancer

Cheetham, S. W., Gruhl, F., Mattick, J. S. and Dinger, M. E. (2013) Long noncoding RNAs and the genetics of cancer. British Journal of Cancer, 108 12: 2419-2425. doi:10.1038/bjc.2013.233


Author Cheetham, S. W.
Gruhl, F.
Mattick, J. S.
Dinger, M. E.
Title Long noncoding RNAs and the genetics of cancer
Journal name British Journal of Cancer   Check publisher's open access policy
ISSN 0007-0920
1532-1827
Publication date 2013-06-01
Year available 2013
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1038/bjc.2013.233
Open Access Status DOI
Volume 108
Issue 12
Start page 2419
End page 2425
Total pages 7
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1306 Cancer Research
2730 Oncology
Abstract Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks. These data reveal a mechanism for the involvement of this region in breast cancer.
Formatted abstract
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.
Keyword Gwas
lncRNA
Cancer heritability
Regulatory RNA
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2014 Collection
UQ Diamantina Institute Publications
 
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