Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif
Hamilton, Mark P.
Hartig, Sean M.
McLellan, Michael D.
Gunaratne, Preethi H.
Wheeler, David A.
McGuire, Sean E.Note: Order does not necessarily reflect citation order of authors.
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CitationHamilton, M. P., K. Rajapakshe, S. M. Hartig, B. Reva, M. D. McLellan, C. Kandoth, L. Ding, et al. 2013. “Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif.” Nature Communications 4 (1): 2730. doi:10.1038/ncomms3730. http://dx.doi.org/10.1038/ncomms3730.
AbstractMicroRNAs 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879197