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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
Nature communications | 2013

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.

Pubmed ID: 24220575

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: P30-DK079638
  • Agency: NCI NIH HHS, United States
    Id: P30CA125123
  • Agency: NCI NIH HHS, United States
    Id: P30 CA125123
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK079638
  • Agency: NIDDK NIH HHS, United States
    Id: K01 DK096093
  • Agency: NIDDK NIH HHS, United States
    Id: 1K01DK096093
  • Agency: NHGRI NIH HHS, United States
    Id: U54 HG003079

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