In vivo identification of tumor- suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma
- PMID: 22000016
- PMCID: PMC3236086
- DOI: 10.1016/j.cell.2011.09.032
In vivo identification of tumor- suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma
Erratum in
- Cell. 2011 Nov 11;147(4):948
Abstract
We recently proposed that competitive endogenous RNAs (ceRNAs) sequester microRNAs to regulate mRNA transcripts containing common microRNA recognition elements (MREs). However, the functional role of ceRNAs in cancer remains unknown. Loss of PTEN, a tumor suppressor regulated by ceRNA activity, frequently occurs in melanoma. Here, we report the discovery of significant enrichment of putative PTEN ceRNAs among genes whose loss accelerates tumorigenesis following Sleeping Beauty insertional mutagenesis in a mouse model of melanoma. We validated several putative PTEN ceRNAs and further characterized one, the ZEB2 transcript. We show that ZEB2 modulates PTEN protein levels in a microRNA-dependent, protein coding-independent manner. Attenuation of ZEB2 expression activates the PI3K/AKT pathway, enhances cell transformation, and commonly occurs in human melanomas and other cancers expressing low PTEN levels. Our study genetically identifies multiple putative microRNA decoys for PTEN, validates ZEB2 mRNA as a bona fide PTEN ceRNA, and demonstrates that abrogated ZEB2 expression cooperates with BRAF(V600E) to promote melanomagenesis.
Copyright © 2011 Elsevier Inc. All rights reserved.
Figures
Comment in
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Epigenetics. Layer by layer.Nat Rev Cancer. 2011 Nov 3;11(12):830. doi: 10.1038/nrc3172. Nat Rev Cancer. 2011. PMID: 22048565 No abstract available.
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Regulatory RNA: layer by layer.Nat Rev Genet. 2011 Nov 3;12(12):804. doi: 10.1038/nrg3108. Nat Rev Genet. 2011. PMID: 22048663 No abstract available.
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RNA: a new layer of regulation.Nat Rev Mol Cell Biol. 2011 Nov 3;12(12):766. doi: 10.1038/nrm3225. Nat Rev Mol Cell Biol. 2011. PMID: 22048709 No abstract available.
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ceRNAs: miRNA target mimic mimics.Cell. 2011 Dec 23;147(7):1431-2. doi: 10.1016/j.cell.2011.12.003. Cell. 2011. PMID: 22196719 No abstract available.
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References
-
- Bosenberg M, Muthusamy V, Curley DP, Wang Z, Hobbs C, Nelson B, Nogueira C, Horner JW, 2nd, Depinho R, Chin L. Characterization of melanocyte-specific inducible Cre recombinase transgenic mice. Genesis. 2006;44:262–267. - PubMed
-
- Brose MS, Volpe P, Feldman M, Kumar M, Rishi I, Gerrero R, Einhorn E, Herlyn M, Minna J, Nicholson A, et al. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res. 2002;62:6997–7000. - PubMed
-
- Candeias MM, Malbert-Colas L, Powell DJ, Daskalogianni C, Maslon MM, Naski N, Bourougaa K, Calvo F, Fahraeus R. P53 mRNA controls p53 activity by managing Mdm2 functions. Nat Cell Biol. 2008;10:1098–1105. - PubMed
-
- Collier LS, Carlson CM, Ravimohan S, Dupuy AJ, Largaespada DA. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature. 2005;436:272–276. - PubMed
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