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

doi:10.1038/ncomms3730

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

Research output: Contribution to journal › Article › peer-review

82 Scopus citations

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 language	English
Article number	2730
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms3730
State	Published - 2013

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@article{9a4f719ed06d4c7296506e109d44a4e2,

title = "Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif",

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.",

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

year = "2013",

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journal = "Nature Communications",

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Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif. / Hamilton, Mark P.; Rajapakshe, Kimal; Hartig, Sean M.; Reva, Boris; McLellan, Michael D.; Kandoth, Cyriac; Ding, Li; Zack, Travis I.; Gunaratne, Preethi H.; Wheeler, David A.; Coarfa, Cristian; McGuire, Sean E.

In: Nature communications, Vol. 4, 2730, 2013.

Research output: Contribution to journal › Article › peer-review

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AU - McLellan, Michael D.

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AU - Ding, Li

AU - Zack, Travis I.

AU - Gunaratne, Preethi H.

AU - Wheeler, David A.

AU - Coarfa, Cristian

AU - McGuire, Sean E.

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