Project abstract for group hallmill

Vacuolar Protein Sorting-associated Protein 4A (VPS4A), a Target of miR-16, in Fibroblasts

These researchers used a genetic approach to identify novel microRNA-mediated pathways in end-stage heart failure. An initial bioinformatics approach identified 1305 SNPs in 3'UTR miRNA Target Sites using dbSNP and the exome sequencing project, (ESP5500). The rationale was that the combined presence of a SNP, a miRNA binding site, and miRNA that was regulated in the processes leading to heart failure may lead to the identification of new druggable pathways. From this list of 1305 SNPs, the group carefully prioritized 126 SNPs based on miRNAs and pathways analyses. Initial genotyping using a Sequenom iPlex platform confirmed the SNPs in the miR-16 binding region of VPS4A (rs16958754, MAF=0.009), ADAMTS1 (rs12140, MAF=0.063), and UCP2 (rs59564714, MAF=0.001) in a cohort of end stage heart failure samples from the University of Minnesota and Royal Brompton and Harefield Trust (n=984). The second goal of this study was to test if VPS4A, ADAMTS1, and UCP2 were valid targets of miR-16. Further functional validation of these targets is in progress. Thus, using a combined bioinformatics and molecular approach, the researchers have identified VPS4A, ADAMTS1 and UCP2 as novel targets of miR-16.