title: MicroRNAs in human cancer.
abstract: Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20-23-nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the translation and stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and invasion. miRNA targeting is initiated through specific base-pairing interactions between the 5' end ("seed" region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3' UTR lead to more effective mRNA destabilization. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. To provide a critical overview of miRNA dysregulation in cancer, we first discuss the methods currently available for studying the role of miRNAs in cancer and then review miRNA genomic organization, biogenesis, and mechanism of target recognition, examining how these processes are altered in tumorigenesis. Given the critical role miRNAs play in tumorigenesis processes and their disease specific expression, they hold potential as therapeutic targets and novel biomarkers.
authors: Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
authors: Thalia A
authors: TA
authors: Farazi
authors: Jessica I
authors: JI
authors: Hoell
authors: Pavel
authors: P
authors: Morozov
authors: Thomas
authors: T
authors: Tuschl
mesh_terms: D001483:Base Sequence; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
references: Genes Dev. 2009 Dec 15;23(24):2806-11
references: 20008931
references: Nat Genet. 2005 May;37(5):495-500
references: 15806104
references: Annu Rev Biochem. 2010;79:321-49
references: 20192758
references: Leukemia. 2005 Nov;19(11):2013-6
references: 16167061
references: FEBS Lett. 2005 Oct 31;579(26):5830-40
references: 16153643
references: Mol Cell. 2011 Sep 16;43(6):892-903
references: 21925378
references: Trends Cell Biol. 2008 Oct;18(10):505-16
references: 18774294
references: Breast Cancer Res. 2008;10(2):203
references: 18373886
references: Nat Genet. 2009 Jul;41(7):843-8
references: 19483683
references: Nat Cell Biol. 2010 Oct;12(10):1014-20
references: 20818387
references: Brief Bioinform. 2009 Sep;10(5):490-7
references: 19332473
references: Nature. 2005 Feb 17;433(7027):769-73
references: 15685193
references: Nature. 2003 Dec 18;426(6968):845-9
references: 14685240
references: Cell Cycle. 2008 Aug 15;7(16):2485-92
references: 18719380
references: Cell. 2009 Feb 20;136(4):642-55
references: 19239886
references: Clin Cancer Res. 2008 Mar 1;14(5):1340-8
references: 18316553
references: Cell Cycle. 2006 Oct;5(19):2220-2
references: 17012846
references: Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19291-6
references: 18042700
references: Science. 2008 Apr 4;320(5872):97-100
references: 18292307
references: Genome Res. 2009 Nov;19(11):2009-20
references: 19767416
references: Nat Methods. 2004 Nov;1(2):155-61
references: 15782179
references: Cell. 2007 Dec 14;131(6):1109-23
references: 18083101
references: RNA. 2006 Feb;12(2):187-91
references: 16373485
references: Cancer Res. 2005 Aug 15;65(16):7065-70
references: 16103053
references: Cell. 2007 Dec 28;131(7):1273-86
references: 18155131
references: Nat Rev Mol Cell Biol. 2009 Feb;10(2):126-39
references: 19165215
references: EMBO Rep. 2007 Aug;8(8):763-9
references: 17599088
references: Cancer Res. 2009 Oct 1;69(19):7495-8
references: 19773429
references: Int J Cancer. 2010 Mar 1;126(5):1166-76
references: 19676045
references: Genome Res. 2009 Jan;19(1):92-105
references: 18955434
references: Science. 2001 Oct 26;294(5543):862-4
references: 11679672
references: Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2812-7
references: 19196975
references: Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11755-60
references: 15284443
references: Cell. 2009 Feb 20;136(4):586-91
references: 19239879
references: Curr Biol. 2002 Apr 30;12(9):735-9
references: 12007417
references: Nature. 2000 Feb 24;403(6772):901-6
references: 10706289
references: Cancer Biol Ther. 2007 Aug;6(8):1284-8
references: 17660710
references: Cell. 2007 Apr 20;129(2):303-17
references: 17397913
references: Science. 2007 Mar 16;315(5818):1576-9
references: 17322030
references: Mol Cell. 2007 Jul 6;27(1):91-105
references: 17612493
references: Nature. 2009 Jul 23;460(7254):529-33
references: 19626115
references: Nature. 2010 Jun 24;465(7301):1033-8
references: 20577206
references: Cold Spring Harb Symp Quant Biol. 2006;71:357-64
references: 17381317
references: Nat Cell Biol. 2008 Aug;10(8):987-93
references: 18604195
references: J Cell Sci. 2010 Jun 1;123(Pt 11):1819-23
references: 20484662
references: J Clin Invest. 2009 Aug;119(8):2366-78
references: 19620785
references: Cell Death Differ. 2010 Apr;17(4):633-41
references: 20019750
references: Genome Biol. 2009;10(6):R64
references: 19531210
references: Nature. 2009 Jul 23;460(7254):479-86
references: 19536157
references: Cell Cycle. 2009 Mar 15;8(6):843-52
references: 19221491
references: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2999-3004
references: 14973191
references: Nat Genet. 2006 Dec;38(12):1375-7
references: 17072315
references: Nat Immunol. 2008 Apr;9(4):405-14
references: 18327259
references: Nat Cell Biol. 2007 May;9(5):604-11
references: 17435748
references: Genes Dev. 2009 Nov 15;23(22):2592-7
references: 19875476
references: Nat Genet. 2009 May;41(5):614-8
references: 19363478
references: Cancer Cell. 2010 Sep 14;18(3):282-93
references: 20832755
references: Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3903-8
references: 18308936
references: Cancer Res. 2007 Dec 15;67(24):11612-20
references: 18089790
references: Breast Cancer Res. 2010;12(2):201
references: 20346098
references: Cancer Cell. 2006 Mar;9(3):189-98
references: 16530703
references: Breast Cancer Res Treat. 2009 Nov;118(1):185-96
references: 18777135
references: Genes Dev. 1991 Oct;5(10):1813-24
references: 1916264
references: Sci Signal. 2010 Apr 13;3(117):ra29
references: 20388916
references: Nature. 2010 Aug 12;466(7308):835-40
references: 20703300
references: Nature. 2005 Jun 9;435(7043):828-33
references: 15944707
references: Nat Genet. 2007 May;39(5):673-7
references: 17401365
references: RNA. 2010 Nov;16(11):2043-50
references: 20855538
references: Nature. 2005 Dec 1;438(7068):685-9
references: 16258535
references: Nat Rev Mol Cell Biol. 2008 Mar;9(3):219-30
references: 18270516
references: Mol Cell Biol. 2007 Mar;27(6):2240-52
references: 17242205
references: RNA. 2008 Aug;14(8):1539-49
references: 18566191
references: Trends Cell Biol. 2008 Aug;18(8):357-9
references: 18585040
references: Nucleic Acids Res. 2008 Mar;36(4):1153-62
references: 18158304
references: Proc Natl Acad Sci U S A. 1989 Nov;86(22):8867-71
references: 2682663
references: Nature. 2010 Jun 3;465(7298):584-9
references: 20424607
references: Cancer Sci. 2011 Jan;102(1):9-17
references: 20735434
references: J Gastroenterol. 2009;44(6):556-61
references: 19363643
references: Cancer Res. 2007 Sep 15;67(18):8699-707
references: 17875710
references: Nat Methods. 2011 Sep 04;8(10):841-3
references: 21892151
references: RNA. 2008 Dec;14(12):2580-96
references: 18978028
references: Cell Res. 2009 Apr;19(4):439-48
references: 19238171
references: Annu Rev Pharmacol Toxicol. 2011;51:25-43
references: 20809797
references: Gynecol Oncol. 2009 Sep;114(3):457-64
references: 19501389
references: Mol Cell. 2007 Jun 8;26(5):745-52
references: 17540599
references: Genome Res. 2010 May;20(5):589-99
references: 20439436
references: Cancer Res. 2004 Jun 1;64(11):3753-6
references: 15172979
references: Clin Cancer Res. 2009 Aug 15;15(16):5060-72
references: 19671845
references: Science. 2001 Oct 26;294(5543):853-8
references: 11679670
references: Int J Cancer. 2009 Feb 1;124(3):568-77
references: 18973228
references: Cell. 1993 Dec 3;75(5):843-54
references: 8252621
references: J Biol Chem. 2008 Aug 1;283(31):21310-4
references: 18550544
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D154-8
references: 17991681
references: Nat Rev Genet. 2009 Feb;10(2):94-108
references: 19148191
references: Cell. 2006 Jun 16;125(6):1111-24
references: 16777601
references: Cell. 1993 Dec 3;75(5):855-62
references: 8252622
references: N Engl J Med. 2005 Oct 27;353(17):1793-801
references: 16251535
references: Nat Rev Cancer. 2007 Nov;7(11):819-22
references: 17914404
references: Nature. 2009 Jun 18;459(7249):1010-4
references: 19458619
references: J Pathol. 2008 Dec;216(4):418-27
references: 18925646
references: Cancer Cell. 2010 Oct 19;18(4):303-15
references: 20951941
references: Nucleic Acids Res. 2007;35(9):2885-92
references: 17439965
references: J Mol Biol. 2010 Sep 24;402(3):491-509
references: 20678503
references: Nat Rev Genet. 2010 Sep;11(9):597-610
references: 20661255
references: Nucleic Acids Res. 2011 Nov 1;39(20):e136
references: 21835775
references: Mol Cancer. 2008 Apr 28;7:35
references: 18442408
references: Nat Methods. 2008 Sep;5(9):777-9
references: 19160512
references: Genes Dev. 2008 Apr 1;22(7):894-907
references: 18381893
references: Methods Mol Biol. 2010;630:49-64
references: 20300990
references: RNA. 2005 Mar;11(3):241-7
references: 15701730
references: Cancer Res. 2007 Aug 15;67(16):7713-22
references: 17699775
references: Science. 2001 Oct 26;294(5543):858-62
references: 11679671
references: Methods Enzymol. 2007;427:107-22
references: 17720481
references: Blood. 2007 Jun 15;109(12):5079-86
references: 17351108
references: Cancer Res. 2011 Sep 1;71(17):5659-69
references: 21693658
references: Nature. 2005 Jun 9;435(7043):839-43
references: 15944709
references: Cancer Res. 2011 Jul 1;71(13):4443-53
references: 21586611
references: Blood. 2008 Nov 15;112(10):4202-12
references: 18713946
references: Oncogene. 1989 Jan;4(1):51-7
references: 2644611
references: Bioinformatics. 2010 Jan 1;26(1):139-40
references: 19910308
references: Nat Cell Biol. 2010 Mar;12(3):247-56
references: 20173740
references: Nature. 2008 Sep 4;455(7209):58-63
references: 18668040
references: Cell Cycle. 2008 Oct;7(20):3112-8
references: 18927505
references: Cell. 2009 Oct 2;139(1):112-22
references: 19804757
references: Genes Dev. 2009 Dec 1;23(23):2700-4
references: 19903759
references: Genes Dev. 2009 Jun 1;23(11):1327-37
references: 19487573
references: Cancer Res. 2010 Apr 15;70(8):3119-27
references: 20354188
references: J Biol Chem. 2004 Dec 10;279(50):52361-5
references: 15504739
references: Nature. 2005 Jun 9;435(7043):834-8
references: 15944708
references: Cancer Res. 2009 Mar 15;69(6):2287-95
references: 19244118
references: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13021-6
references: 18755890
references: Biotechniques. 2003 Jan;34(1):88-91
references: 12545545
references: Cell. 2010 Apr 2;141(1):129-41
references: 20371350
references: RNA. 2007 Oct;13(10):1668-74
references: 17698639
references: Cell. 2007 Jun 29;129(7):1401-14
references: 17604727
references: Cell. 2009 Jan 23;136(2):215-33
references: 19167326
references: Nat Rev Genet. 2011 Feb;12(2):99-110
references: 21245828
references: Int J Cancer. 2011 Mar 15;128(6):1327-34
references: 20473948
references: Mol Cell. 2007 Oct 26;28(2):328-36
references: 17964270
references: Mol Cancer Res. 2008 May;6(5):735-42
references: 18505919
references: Nat Methods. 2009 Feb;6(2):139-41
references: 19137005
references: Nat Genet. 2010 Oct;42(10):817-8; author reply 818
references: 20877318
references: Nat Rev Mol Cell Biol. 2009 Feb;10(2):141-8
references: 19145236
references: Science. 2010 Jan 8;327(5962):198-201
references: 19965718
references: Nat Genet. 2009 Mar;41(3):365-70
references: 19219043
references: Methods. 2008 Jan;44(1):13-21
references: 18158128
references: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15524-9
references: 12434020
references: Int J Cancer. 2007 Sep 1;121(5):1156-61
references: 17487835
references: Genome Biol. 2010;11(11):141
references: 21118581
references: RNA. 2011 Sep;17(9):1697-712
references: 21775473
references: Cell Death Differ. 2010 Feb;17(2):215-20
references: 19498445
references: J Biol Chem. 2009 Jul 3;284(27):18515-24
references: 19419954
references: Biotechnol Lett. 2010 Dec;32(12):1777-88
references: 20703800
references: Oncogene. 2007 Nov 29;26(54):7590-5
references: 17563749
references: Dev Cell. 2003 Aug;5(2):351-8
references: 12919684
references: J Thorac Cardiovasc Surg. 2008 Feb;135(2):255-60; discussion 260
references: 18242245
references: Cancer Sci. 2010 Nov;101(11):2309-15
references: 20726859
references: Cancer Res. 2008 Oct 15;68(20):8535-40
references: 18922928
references: Silence. 2010 Jan 12;1(1):3
references: 20226069
references: Cell. 2009 Jun 12;137(6):1005-17
references: 19524505
references: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
references: 11309499
references: Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15163-8
references: 20699384
references: Cell. 2009 Aug 21;138(4):673-84
references: 19703394
references: Cell Metab. 2006 Feb;3(2):87-98
references: 16459310
references: J Pathol. 2008 Jan;214(1):17-24
references: 17948228
references: Genes Dev. 2010 May 15;24(10):992-1009
references: 20413612
references: Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):498-502
references: 19114655
references: Genes Dev. 2009 Aug 1;23(15):1743-8
references: 19574298
references: Oncogene. 2010 Apr 15;29(15):2302-8
references: 20190813
references: Nature. 2008 Jul 3;454(7200):56-61
references: 18548003
references: RNA. 2009 Dec;15(12):2375-84
references: 19861428
references: Cancer Cell. 2006 Jun;9(6):435-43
references: 16766263
references: Nat Rev Cancer. 2010 Jun;10(6):389-402
references: 20495573
references: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2183-8
references: 20080666
references: Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5166-71
references: 18362358
references: Curr Drug Targets. 2010 Aug;11(8):926-35
references: 20415649
references: RNA. 2008 May;14(5):844-52
references: 18375788
references: Cell. 2004 Jan 23;116(2):281-97
references: 14744438
references: Gynecol Oncol. 2010 Jan;116(1):117-25
references: 19854497
references: Nature. 2008 Apr 17;452(7189):896-9
references: 18368051
references: Cell. 2005 Aug 26;122(4):553-63
references: 16122423
references: BMC Biol. 2010 May 11;8:58
references: 20459774
references: J Pathol. 2010 Sep;222(1):41-51
references: 20593407
references: Cell. 2010 Feb 19;140(4):445-9
references: 20178735
references: Nature. 2008 Sep 4;455(7209):64-71
references: 18668037
references: Nat Cell Biol. 2010 Apr;12(4):372-9
references: 20190740
references: Genome Res. 2004 Dec;14(12):2486-94
references: 15574827
references: RNA. 2010 May;16(5):991-1006
references: 20360395
references: Nature. 2010 Sep 2;467(7311):86-90
references: 20693987
references: Cancer Lett. 2009 Mar 8;275(1):44-53
references: 19006648
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D152-7
references: 21037258
references: Nat Cell Biol. 2009 Mar;11(3):228-34
references: 19255566
references: Nat Genet. 2011 Sep 04;43(10):1026-30
references: 21892160
references: Nat Genet. 2009 May;41(5):609-13
references: 19363479
references: Proc Natl Acad Sci U S A. 2006 May 2;103(18):7024-9
references: 16641092
references: Nat Rev Cancer. 2011 Aug 05;11(9):644-56
references: 21822212
references: Nature. 2004 Sep 16;431(7006):343-9
references: 15372041
references: J Exp Med. 2008 Mar 17;205(3):585-94
references: 18299402
references: Nat Struct Mol Biol. 2009 Oct;16(10):1021-5
references: 19713958
references: Genes Dev. 2008 Oct 15;22(20):2773-85
references: 18923076
references: Cell. 2008 Apr 18;133(2):217-22
references: 18423194