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 - Funding Information:
We gratefully acknowledge the contributions from the TCGA Research Network and its TCGA Pan-Cancer Analysis Working Group (contributing consortium members are listed in the Supplementary Note 1). The TCGA Pan-Cancer Analysis Working Group is coordinated by J.M. Stuart, C. Sander and I. Shmulevich. This work was supported by the Caroline Wiess Law Foundation (S.E.M); Dan L. Duncan Cancer Center Scholar Award (S.E.M); S.E.M. is a member of the Dan L. Duncan Cancer Center supported by the National Cancer Institute Cancer Center Support Grant P30CA125123. We acknowledge the joint participation by the Diana Helis Henry Medical Research Foundation through its direct engagement in the continuous active conduct of medical research in conjunction with Baylor College of Medicine Baylor Research Advocates for Student Scientists (BRASS) Foundation (M.P.H); the Robert and Janice McNair Foundation (M.P.H); and NIH 1K01DK096093 (S.M.H.) with additional funding provided by the Diabetes and Endocrinology Research Center (P30-DK079638) at Baylor College of Medicine. A special thanks to Kat Harris and the Switchgear Genomics team for fast, efficient and kind service. We thank Robb Moses, David Bader and Joel Neilson for editing contributions.
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 -