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Nature Reviews Cancer | AOP, published online 15 July 2010; doi:10.1038/nrc2898

SmALL RNAS

Pseudogenes act as microRNA decoys


A recent study revises our view of Furthermore, in prostate cancer How widespread is this
pseudogenes as non-functional relics cells, expression of PTEN-targeting mechanism of regulating cancer
of evolution by showing that tran- miRNAs led to downregulation of genes? The authors found miRNA-
scripts produced from pseudogenes both PTEN and PTENP1 mRNAs, binding sites in pseudogenes of
regulate the effects of microRNAs confirming that PTENP1 is subject other cancer-related genes. They also
(miRNAs). to miRNA-mediated regulation. demonstrated a similar relationship
Poliseno, Salmena et al. inves- Does miRNA binding by PTENP1 between the oncogene KRAS and its
tigated PTENP1, a pseudogene of affect the tumour suppressive activi- pseudogene KRAS1P to that between
the tumour suppressor gene PTEN. ties of PTEN? Overexpression of PTEN and PTENP1. Because each
They found several binding sites the PTENP1 3′ untranslated region miRNA has multiple targets and
for miRNAs that target PTEN in (UTR) led to increased levels of because genes can often have several
the 3′ UTR of PTENP1 mRNA. PTEN transcripts and protein and to related pseudogenes, complex
growth inhibition in prostate cancer networks of regulation may exist.
cells. This derepression of PTEN by This decoy mechanism may not be
the PTENP1 3′ UTR was abrogated limited to pseudogene transcripts,
in DICER-null colon carcinoma so the next steps will be to inves-
cells, which are defective in miRNA tigate whether other gene-coding
IMAGE SOURCE

processing. These findings suggest and non-coding RNAs can act as


that mature miRNAs are needed for trans-regulators by miRNA binding
PTENP1 to regulate PTEN levels. and how generally this mechanism
The authors also identified focal applies outside of cancer genes. The
copy number losses at the PTENP1 insights from this study may also
locus associated with downregulation help to identify new therapeutic
of PTEN expression in samples from targets in cancer.
patients with sporadic colon cancer. Meera Swami
They suggest that PTENP1 could be
considered a tumour suppressor ORIGINAL RESEARCH PAPER Poliseno, L. et al.
gene and that there might be A coding-independent function of gene and
selection for loss of PTENP1 during pseudogene mRNAs regulates tumour biology.
Nature 465, 1033–1038 (2010)
tumorigenesis.

NATURE REviEwS | cANceR vOlUmE 10 | AUgUST 2010

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