biostudies-literatureHamilton MPNIDDK NIH HHSNHGRI NIH HHSNCI NIH HHS2730https://www.ebi.ac.uk/biostudies/studies/S-EPMC3868236biostudies-literatureUnknown4MicroRNAs modulate tumorigenesis through suppression of specific genes. As many tumour types rely on overlapping oncogenic pathways, a core set of microRNAs may exist, which consistently drives or suppresses tumorigenesis in many cancer types. Here we integrate The Cancer Genome Atlas (TCGA) pan-cancer data set with a microRNA target atlas composed of publicly available Argonaute Crosslinking Immunoprecipitation (AGO-CLIP) data to identify pan-tumour microRNA drivers of cancer. Through this analysis, we show a pan-cancer, coregulated oncogenic microRNA 'superfamily' consisting of the miR-17, miR-19, miR-130, miR-93, miR-18, miR-455 and miR-210 seed families, which cotargets critical tumour suppressors via a central GUGC core motif. We subsequently define mutations in microRNA target sites using the AGO-CLIP microRNA target atlas and TCGA exome-sequencing data. These combined analyses identify pan-cancer oncogenic cotargeting of the phosphoinositide 3-kinase, TGF? and p53 pathways by the miR-17-19-130 superfamily members.Nature communicationsIdentification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif.PMC3868236P30CA125123P30 DK0796381K01DK096093K01 DK096093U54 HG003079P30-DK079638P30 CA125123Hamilton MPHartig SMReva BGunaratne PHCoarfa CRajapakshe KMcLellan MDMcGuire SEWheeler DAKandoth CZack TIDing LfalseIdentification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif.MicroRNAs modulate tumorigenesis through suppression of specific genes. As many tumour types rely on overlapping oncogenic pathways, a core set of microRNAs may exist, which consistently drives or suppresses tumorigenesis in many cancer types. Here we integrate The Cancer Genome Atlas (TCGA) pan-cancer data set with a microRNA target atlas composed of publicly available Argonaute Crosslinking Immunoprecipitation (AGO-CLIP) data to identify pan-tumour microRNA drivers of cancer. Through this analysis, we show a pan-cancer, coregulated oncogenic microRNA 'superfamily' consisting of the miR-17, miR-19, miR-130, miR-93, miR-18, miR-455 and miR-210 seed families, which cotargets critical tumour suppressors via a central GUGC core motif. We subsequently define mutations in microRNA target sites using the AGO-CLIP microRNA target atlas and TCGA exome-sequencing data. These combined analyses identify pan-cancer oncogenic cotargeting of the phosphoinositide 3-kinase, TGF? and p53 pathways by the miR-17-19-130 superfamily members.2013-01-01T00:00:00Z20132020-11-19T15:16:57Z2019-03-27T01:18:44ZS-EPMC38682362422057510.1038/ncomms3730