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

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

Friday, 14.02.2020

 

Authors and Affiliations:

Ana Jacinta-Fernandes, Joana M. Xavier, Ramiro Magno, Joel G. Lage & Ana-Teresa Maia

Centre for Biomedical Research (CBMR), Algarve Biomedical Center (ABC) and Department of Biomedical Sciences and Medicine (DCBM) Universidade do Algarve, Faro 8005-139, Portugal

 

Abstract:

Most breast cancer (BC) risk-associated single-nucleotide polymorphisms (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 microRNA (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≤5×10−8) 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 3′-untranslated regions of putative miRNA target genes were predicted to alter miRNA::mRNA (messenger RNA) 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 reinforce 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.

 

Journal: npj Genomic Medicine

 

Linkhttps://www.nature.com/articles/s41525-019-0112-9