TY - JOUR
T1 - Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif
AU - Hamilton, Mark P.
AU - Rajapakshe, Kimal
AU - Hartig, Sean M.
AU - Reva, Boris
AU - McLellan, Michael D.
AU - Kandoth, Cyriac
AU - Ding, Li
AU - Zack, Travis I.
AU - Gunaratne, Preethi H.
AU - Wheeler, David A.
AU - Coarfa, Cristian
AU - McGuire, Sean E.
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84887641104&partnerID=8YFLogxK
U2 - 10.1038/ncomms3730
DO - 10.1038/ncomms3730
M3 - Article
C2 - 24220575
AN - SCOPUS:84887641104
VL - 4
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 2730
ER -