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Nat Commun. 2013;4:2730. doi: 10.1038/ncomms3730.

Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif.

Author information

1
Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza Houston M822, Houston, Texas 77030, USA.

Abstract

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, TGFβ and p53 pathways by the miR-17-19-130 superfamily members.

PMID:
24220575
PMCID:
PMC3868236
DOI:
10.1038/ncomms3730
[Indexed for MEDLINE]
Free PMC Article
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