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 and Sean E. McGuire ()
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Mark P. Hamilton: Baylor College of Medicine, 1 Baylor Plaza Houston M822, Houston, Texas 77030, USA
Kimal Rajapakshe: Baylor College of Medicine, 1 Baylor Plaza Houston M822, Houston, Texas 77030, USA
Sean M. Hartig: Baylor College of Medicine, 1 Baylor Plaza Houston M822, Houston, Texas 77030, USA
Boris Reva: Computational Biology Center, Memorial Sloan Kettering Cancer Center
Michael D. McLellan: The Genome Institute, Washington University
Cyriac Kandoth: The Genome Institute, Washington University
Li Ding: The Genome Institute, Washington University
Travis I. Zack: The Eli and Edythe L Broad Institute of Massachusetts Institute of Technology and Harvard University
Preethi H. Gunaratne: University of Houston, 4800 Calhoun
David A. Wheeler: The Human Genome Sequencing Center, Baylor College of Medicine
Cristian Coarfa: Baylor College of Medicine, 1 Baylor Plaza Houston M822, Houston, Texas 77030, USA
Sean E. McGuire: Baylor College of Medicine, 1 Baylor Plaza Houston M822, Houston, Texas 77030, USA

Nature Communications, 2013, vol. 4, issue 1, 1-13

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3730

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