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

Mark P. Hamilton, Kimal Rajapakshe, Sean M. Hartig, Boris Reva, Michael D. McLellan, Cyriac Kandoth, Li Ding, Travis I. Zack, Preethi H. Gunaratne, David A. Wheeler, Cristian Coarfa, Sean E. McGuire

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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.

Original languageEnglish
Article number2730
JournalNature communications
Volume4
DOIs
StatePublished - Jan 1 2013

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    Hamilton, M. P., Rajapakshe, K., Hartig, S. M., Reva, B., McLellan, M. D., Kandoth, C., Ding, L., Zack, T. I., Gunaratne, P. H., Wheeler, D. A., Coarfa, C., & McGuire, S. E. (2013). Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif. Nature communications, 4, [2730]. https://doi.org/10.1038/ncomms3730