4.5 Article

Analysis of microRNA-target interactions across diverse cancer types

Journal

NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 20, Issue 11, Pages 1325-U131

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2678

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Funding

  1. Danish Research Council
  2. Lundbeck Foundation
  3. Carlsberg Foundation
  4. Sidney Kimmel Foundation
  5. Sontag Foundation
  6. TCGA Genome Data Analysis Center [U24 CA143840]
  7. Christian og Ottilia Brorsons Rejselegat for Yngre Videnskabsmaend og kvinder

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Little is known about the extent to which individual microRNAs ( miRNAs) regulate common processes of tumor biology across diverse cancer types. Using molecular profiles of >3,000 tumors from 11 human cancer types in The Cancer Genome Atlas, we systematically analyzed expression of miRNAs and mRNAs across cancer types to infer recurrent cancer-associated miRNA-target relationships. As we expected, the inferred relationships were consistent with sequence-based predictions and published data from miRNA perturbation experiments. Notably, miRNAs with recurrent target relationships were frequently regulated by genetic and epigenetic alterations across the studied cancer types. We also identify new examples of miRNAs that coordinately regulate cancer pathways, including the miR-29 family, which recurrently regulates active DNA demethylation pathway members TET1 and TDG. The online resource http://cancerminer.org allows exploration and prioritization of miRNA-target interactions that potentially regulate tumorigenesis.

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