Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif

Nat Commun. 2013;4:2730. doi: 10.1038/ncomms3730.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Algorithms
  • Amino Acid Motifs
  • Carcinogenesis
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Humans
  • MicroRNAs / metabolism*
  • Multigene Family
  • Mutation
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / metabolism
  • Transforming Growth Factor beta / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • RNA, Messenger
  • TP53 protein, human
  • Transforming Growth Factor beta
  • Tumor Suppressor Protein p53
  • Phosphatidylinositol 3-Kinases