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RNA

A new layer of regulation

Nature Reviews Molecular Cell Biology volume 12, page 766 (2011)Cite this article

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Three of the studies focused on the tumour suppressor phosphatase and tensin homologue (PTEN), the expression of which is altered in many human cancers, and examined how it might be regulated by ceRNAs. Using a range of approaches, the authors identified RNAs that may be interacting with PTEN RNA, some of which were co-expressed with PTEN in cells from patients with prostate cancer (Tay et al.), glioblastoma (Sumazin et al.) or melanoma (Karreth et al.). Interestingly, in all three studies, a subset of these transcripts positively modulated the expression of PTEN RNA, as their knockdown was accompanied by a significant reduction in PTEN RNA levels. This regulation was reciprocal, with depletion of PTEN RNA leading to a decrease in the levels of the studied transcripts.

The ceRNA hypothesis postulates that interactions between RNAs are mediated by competitive binding of these RNAs to miRNAs — this was in fact one of the principles used by Sumazin et al. to identify candidate miRNA-mediated interactions, including more than 500 PTEN-regulating RNAs. Consistently, Tay et al. and Karreth et al. showed that, in the absence of miRNAs, depletion of ceRNAs does not affect the expression of PTEN RNA, indicating that the RNA–RNA interaction is miRNA dependent.

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References

ORIGINAL RESEARCH PAPERS

  1. Tay, Y. et al. Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell 147, 344–357 (2011) Article

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  2. Sumazin, P. et al. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell 147, 370–381 (2011) Article

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  3. Karreth, F. A. et al. In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell 147, 382–395 (2011) Article

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  4. Cesana, M. et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147, 358–369 (2011) Article

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FURTHER READING

  1. Salmena, L. et al. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146, 353–358 (2011)

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  2. Poliseno, L. et al. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465, 1033–1038 (2010)

    Article  CAS  Google Scholar 

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Authors
  1. Rachel David
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David, R. A new layer of regulation. Nat Rev Mol Cell Biol 12, 766 (2011). https://doi.org/10.1038/nrm3225

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