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Cell. 2011 Oct 14;147(2):344-57. doi: 10.1016/j.cell.2011.09.029.

Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs.

Author information

  • 1Cancer Genetics Program, Division of Genetics, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Here, we demonstrate that protein-coding RNA transcripts can crosstalk by competing for common microRNAs, with microRNA response elements as the foundation of this interaction. We have termed such RNA transcripts as competing endogenous RNAs (ceRNAs). We tested this hypothesis in the context of PTEN, a key tumor suppressor whose abundance determines critical outcomes in tumorigenesis. By a combined computational and experimental approach, we identified and validated endogenous protein-coding transcripts that regulate PTEN, antagonize PI3K/AKT signaling, and possess growth- and tumor-suppressive properties. Notably, we also show that these genes display concordant expression patterns with PTEN and copy number loss in cancers. Our study presents a road map for the prediction and validation of ceRNA activity and networks and thus imparts a trans-regulatory function to protein-coding mRNAs.

Copyright © 2011 Elsevier Inc. All rights reserved.

Comment in

  • Epigenetics. Layer by layer. [Nat Rev Cancer. 2011]
  • RNA: a new layer of regulation. [Nat Rev Mol Cell Biol. 2011]
  • ceRNAs: miRNA target mimic mimics. [Cell. 2011]
  • Regulatory RNA: layer by layer. [Nat Rev Genet. 2011]
PMID:
22000013
[PubMed - indexed for MEDLINE]
PMCID:
PMC3235920
Free PMC Article

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