title: Emerging roles of competing endogenous RNAs in cancer: insights from the regulation of PTEN.
abstract: The capacity of noncoding RNA to regulate gene expression in health and disease is epitomized by the microRNAs, small ∼22-nucleotide RNAs that target mRNAs to repress their translation into protein. Recently a previously unrecognized gene regulatory layer has emerged, characterized by the ability of a wide range of RNA transcripts to vie for microRNA binding and alleviate the repressive effect of microRNAs on their mRNA targets. Termed competing endogenous RNAs (ceRNAs), these participate in a microRNA-dependent cross talk, producing robust networks that when perturbed may lead to cancer. To date, the tumor suppressor PTEN has been most extensively validated as competing with a variety of ceRNAs in different cancers: reducing these ceRNAs appears to reduce PTEN levels, tipping cells toward cancer progression. In this review we look at ceRNA networks in cancer, their characteristics, and constituent parts, focusing on the insights that can be gained from the studies conducted on PTEN. We also explore the conditions that facilitate ceRNA cross talk, proposing that the disruption of these conditions may represent a general phenomenon in carcinogenesis.
authors.affiliation: Division of Oncology, Department of Surgery and Cancer, Imperial Centre for Translational and Experimental Medicine, Imperial College, London, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: de Giorgio
authors.forename: Jonathan
authors.initials: J
authors.lastname: Krell
authors.forename: Victoria
authors.initials: V
authors.lastname: Harding
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.forename: Leandro
authors.initials: L
authors.lastname: Castellano
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
references.citation: Mol Cell. 2011 Aug 5;43(3):327-39
references.pmid: 21723170
references.citation: Nat Rev Genet. 2004 May;5(5):396-400
references.pmid: 15143321
references.citation: Nat Rev Genet. 2009 Aug;10(8):578-85
references.pmid: 19609263
references.citation: Curr Biol. 2009 May 26;19(10):870-3
references.pmid: 19375315
references.citation: Nucleic Acids Res. 2011 Apr;39(8):3026-41
references.pmid: 21149267
references.citation: Cancer Res. 2008 May 15;68(10):3566-72
references.pmid: 18483236
references.citation: Nucleic Acids Res. 2005 Apr 28;33(8):2374-83
references.pmid: 15860774
references.citation: Dev Cell. 2013 Apr 15;25(1):69-80
references.pmid: 23541921
references.citation: Nature. 2009 Mar 12;458(7235):223-7
references.pmid: 19182780
references.citation: Nature. 2008 Sep 4;455(7209):64-71
references.pmid: 18668037
references.citation: Cell. 2011 Oct 14;147(2):344-57
references.pmid: 22000013
references.citation: Nat Struct Mol Biol. 2013 Apr;20(4):440-6
references.pmid: 23435381
references.citation: Nat Rev Mol Cell Biol. 2009 Feb;10(2):126-39
references.pmid: 19165215
references.citation: Cell. 2012 Nov 9;151(4):765-777
references.pmid: 23102813
references.citation: PLoS One. 2012;7(2):e30733
references.pmid: 22319583
references.citation: Genome Res. 2012 Dec;22(12):2418-26
references.pmid: 22855835
references.citation: Nat Genet. 2011 Aug 21;43(9):854-9
references.pmid: 21857679
references.citation: Science. 2012 Apr 13;336(6078):233-7
references.pmid: 22422859
references.citation: Nature. 2010 Jun 24;465(7301):1033-8
references.pmid: 20577206
references.citation: Nature. 2009 Jul 23;460(7254):479-86
references.pmid: 19536157
references.citation: Cell. 2010 Oct 1;143(1):46-58
references.pmid: 20887892
references.citation: Science. 2007 Jun 8;316(5830):1484-8
references.pmid: 17510325
references.citation: Nat Protoc. 2012 Jul 26;7(8):1534-50
references.pmid: 22836135
references.citation: Nat Rev Genet. 2007 Jun;8(6):413-23
references.pmid: 17486121
references.citation: Cell. 2011 Oct 14;147(2):382-95
references.pmid: 22000016
references.citation: Genes Dev. 2012 Jan 1;26(1):43-53
references.pmid: 22215810
references.citation: Nucleic Acids Res. 2013 Mar 1;41(5):3339-51
references.pmid: 23325850
references.citation: Cancer Sci. 2005 Feb;96(2):111-5
references.pmid: 15723655
references.citation: Science. 2010 Jun 18;328(5985):1563-6
references.pmid: 20558719
references.citation: Science. 2010 Jun 18;328(5985):1534-9
references.pmid: 20558712
references.citation: Nature. 2010 Aug 12;466(7308):835-40
references.pmid: 20703300
references.citation: Nat Genet. 2007 May;39(5):673-7
references.pmid: 17401365
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16230-5
references.pmid: 18852463
references.citation: Nat Genet. 2010 Dec;42(12):1113-7
references.pmid: 21057500
references.citation: Mol Cell. 2010 May 14;38(3):323-32
references.pmid: 20471939
references.citation: Nature. 1996 Jan 11;379(6561):131-7
references.pmid: 8538762
references.citation: Nat Biotechnol. 2009 Jun;27(6):549-55
references.pmid: 19465925
references.citation: Mol Cell Biol. 2006 Aug;26(15):5744-58
references.pmid: 16847328
references.citation: Cell. 2011 Oct 14;147(2):358-69
references.pmid: 22000014
references.citation: Nature. 2012 Jun 28;486(7404):541-4
references.pmid: 22722835
references.citation: Cell. 2006 Jun 16;125(6):1111-24
references.pmid: 16777601
references.citation: Cell. 2007 Jun 29;129(7):1311-23
references.pmid: 17604720
references.citation: Nature. 2010 Apr 15;464(7291):1071-6
references.pmid: 20393566
references.citation: Nat Genet. 2007 Aug;39(8):1033-7
references.pmid: 17643101
references.citation: Genes Dev. 2012 Jul 1;26(13):1459-72
references.pmid: 22751500
references.citation: Genome Biol. 2012 Aug 28;13(8):R75
references.pmid: 22929540
references.citation: Mol Syst Biol. 2010 Apr 20;6:363
references.pmid: 20404830
references.citation: Dev Biol. 1999 Dec 15;216(2):671-80
references.pmid: 10642801
references.citation: Cancer Res. 2008 Oct 15;68(20):8195-200
references.pmid: 18922890
references.citation: Nat Rev Genet. 2010 Sep;11(9):597-610
references.pmid: 20661255
references.citation: Bioinformation. 2012;8(15):731-3
references.pmid: 23055620
references.citation: Curr Biol. 2010 Oct 12;20(19):R858-61
references.pmid: 20937476
references.citation: Nat Genet. 2010 May;42(5):454-8
references.pmid: 20400965
references.citation: Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7154-9
references.pmid: 23536298
references.citation: Curr Opin Microbiol. 2008 Dec;11(6):574-9
references.pmid: 18935980
references.citation: Clin Biochem. 2010 Feb;43(3):324-7
references.pmid: 19782670
references.citation: Cell. 2011 Aug 5;146(3):353-8
references.pmid: 21802130
references.citation: Nature. 2013 Mar 21;495(7441):333-8
references.pmid: 23446348
references.citation: Science. 2007 Sep 21;317(5845):1764-7
references.pmid: 17656684
references.citation: Nature. 2005 Jun 9;435(7043):834-8
references.pmid: 15944708
references.citation: Cell. 2011 Oct 14;147(2):370-81
references.pmid: 22000015
references.citation: Cell. 2010 Apr 2;141(1):129-41
references.pmid: 20371350
references.citation: Curr Biol. 2011 Mar 8;21(5):369-76
references.pmid: 21353554
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: Cell. 2009 Feb 20;136(4):629-41
references.pmid: 19239885
references.citation: Nucleic Acids Res. 2012 Jun;40(11):5088-100
references.pmid: 22362743
references.citation: RNA. 2013 Feb;19(2):141-57
references.pmid: 23249747
references.citation: Nature. 2008 Oct 23;455(7216):1061-8
references.pmid: 18772890
references.citation: Cell. 2009 Aug 21;138(4):673-84
references.pmid: 19703394
references.citation: Mol Cell. 2010 Sep 24;39(6):925-38
references.pmid: 20797886
references.citation: Adv Bioinformatics. 2013;2013:360678
references.pmid: 23573084
references.citation: Nature. 2013 Mar 21;495(7441):384-8
references.pmid: 23446346
references.citation: Genes Dev. 2009 Aug 1;23(15):1743-8
references.pmid: 19574298
references.citation: Nat Genet. 2008 Jan;40(1):43-50
references.pmid: 18066065
references.citation: PLoS One. 2010 Oct 25;5(10):e13599
references.pmid: 21049042
references.citation: PLoS One. 2011;6(7):e22570
references.pmid: 21799901
references.citation: Nat Methods. 2007 Sep;4(9):721-6
references.pmid: 17694064
references.citation: J Mol Biol. 2008 Dec 31;384(5):1106-19
references.pmid: 18938177
references.citation: Nat Rev Cancer. 2011 Aug 05;11(9):644-56
references.pmid: 21822212
references.citation: Biophys J. 2013 Mar 5;104(5):1203-13
references.pmid: 23473503
references.citation: Science. 2005 Sep 2;309(5740):1573-6
references.pmid: 16081698
references.citation: Science. 2008 Jun 20;320(5883):1643-7
references.pmid: 18566288