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bioRxiv · 10.1101/777318

Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk

Jacinta-Fernandes, A. C.·Xavier, J. M.·Magno, R.·Lage, J.·Maia, A.-T.
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Abstract

Most breast cancer (BC) risk-associated variants (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting miRNA genes and/or miRNA-binding. To test this we adapted two miRNA-binding prediction algorithms -- TargetScan and miRanda -- to perform allele-specific queries, and integrated differential allelic expression (DAE) and expression quantitative trait loci (eQTL) data, to query 150 genome-wide significant (P [≤] 5 x 10-8) raSNPs, plus proxies. We found that no raSNP mapped to a miRNA gene, suggesting that altered miRNA targeting is an unlikely mechanism involved in BC risk. Also, 11.5% (6 out of 52) raSNPs located in 3UTRs of putative miRNA target genes were predicted to alter miRNA::mRNA pair binding stability in five candidate target genes. Of these, we propose RNF115, at locus 1q21.1, as a strong novel target gene associated with BC risk, and re-inforce the role of miRNA mediated cis-regulation at locus 19p13.11. We believe that integrating allele-specific querying in miRNA-binding prediction, and data supporting cis-regulation of expression, improves the identification of candidate target genes in BC risk, as well as in other common cancers and complex diseases.

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Jacinta-Fernandes, A. C., Xavier, J. M., Magno, R., Lage, J., Maia, A.-T.. 2019-09-20. Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk. https://doi.org/10.1101/777318

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