title: MicroRNA binding site polymorphisms as biomarkers in cancer management and research.
abstract: MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression. They have been implicated in a broad range of biological processes, and miRNA-related genetic alterations probably underlie several human diseases. Single nucleotide polymorphisms of transcripts may modulate the posttranscriptional regulation of gene expression by miRNAs and explain interindividual variability in cancer risk and in chemotherapy response. On the basis of recent association studies published in the literature, the present review mainly summarizes the potential role of miRNAs as molecular biomarkers for disease susceptibility, diagnosis, prognosis, and drug-response prediction in tumors. Many clues suggest a role for polymorphisms within the 3' untranslated regions of KRAS rs61764370, SET8 rs16917496, and MDM4 rs4245739 as SNPs in miRNA binding sites highly promising in the biology of human cancer. However, more studies are needed to better characterize the composite spectrum of genetic determinants for future use of markers in risk prediction and clinical management of diseases, heading toward personalized medicine.
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cipollini
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Landi
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Gemignani
keywords: 3′-UTR target binding site; biomarkers; cancer risk; miRSNP
references.citation: Haematologica. 2013 Jun;98(6):913-7
references.pmid: 23065518
references.citation: Ann Oncol. 2013 Oct;24 Suppl 6:vi51-6
references.pmid: 24078662
references.citation: Clin Cancer Res. 2013 Jan 1;19(1):34-41
references.pmid: 23262034
references.citation: Mol Biol Rep. 2012 Jan;39(1):369-73
references.pmid: 21556765
references.citation: Nat Genet. 2005 May;37(5):495-500
references.pmid: 15806104
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13653-8
references.pmid: 21810988
references.citation: Nature. 2005 Feb 17;433(7027):769-73
references.pmid: 15685193
references.citation: J Biol Chem. 2002 Oct 18;277(42):39926-36
references.pmid: 12161446
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3300-5
references.pmid: 17360642
references.citation: Eur Cytokine Netw. 2008 Dec;19(4):204-10
references.pmid: 19103527
references.citation: Carcinogenesis. 2012 Feb;33(2):338-47
references.pmid: 22114071
references.citation: Mol Cell Biol. 2009 Apr;29(8):2278-95
references.pmid: 19223465
references.citation: Cancer Lett. 2012 Dec 31;327(1-2):73-89
references.pmid: 22252118
references.citation: Proc Natl Acad Sci U S A. 2011 Feb 22;108(8):3116-23
references.pmid: 21282610
references.citation: PLoS One. 2013 Oct 11;8(10):e77024
references.pmid: 24146953
references.citation: PLoS One. 2012;7(12):e51301
references.pmid: 23284679
references.citation: Cancer Chemother Pharmacol. 2012 Mar;69(3):723-31
references.pmid: 21993663
references.citation: Exp Ther Med. 2012 Apr;3(4):689-692
references.pmid: 22969952
references.citation: J Immunol. 2012 Feb 15;188(4):1573-7
references.pmid: 22262659
references.citation: PLoS Biol. 2004 Nov;2(11):e363
references.pmid: 15502875
references.citation: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W696-700
references.pmid: 15980566
references.citation: Carcinogenesis. 2012 Nov;33(11):2147-54
references.pmid: 22859270
references.citation: World J Gastroenterol. 2008 Jul 21;14(27):4300-8
references.pmid: 18666317
references.citation: Eur J Cardiothorac Surg. 2012 Jun;41(6):e173-81
references.pmid: 22529186
references.citation: Tumour Biol. 2014 Jan;35(1):295-301
references.pmid: 23918301
references.citation: Biochem Biophys Res Commun. 2013 Jan 11;430(2):529-34
references.pmid: 23232114
references.citation: Tumour Biol. 2013 Oct;34(5):3159-63
references.pmid: 23729275
references.citation: J Biol Chem. 2007 Jul 13;282(28):20053-7
references.pmid: 17502368
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7475-9
references.pmid: 9636174
references.citation: PLoS One. 2011;6(6):e21726
references.pmid: 21738780
references.citation: Cancer Res. 2012 Mar 15;72(6):1467-77
references.pmid: 22282660
references.citation: Carcinogenesis. 2013 Oct;34(10):2292-9
references.pmid: 23715500
references.citation: J Clin Oncol. 2009 Aug 10;27(23):3757-63
references.pmid: 19451439
references.citation: Genes Dev. 2004 May 15;18(10):1165-78
references.pmid: 15131085
references.citation: Breast Cancer Res Treat. 2011 Jul;128(1):79-84
references.pmid: 20676756
references.citation: J Cell Sci. 2003 Jul 15;116(Pt 14):2975-86
references.pmid: 12808020
references.citation: Breast Cancer Res Treat. 2013 Jul;140(1):151-7
references.pmid: 23793604
references.citation: Mol Biol Rep. 2013 May;40(5):3493-502
references.pmid: 23277395
references.citation: J Cell Sci. 2005 May 15;118(Pt 10):2085-92
references.pmid: 15890984
references.citation: Nat Cell Biol. 2010 Nov;12(11):1086-93
references.pmid: 20953199
references.citation: Carcinogenesis. 2012 Mar;33(3):581-6
references.pmid: 22166496
references.citation: Cancer Res. 1980 Apr;40(4):998-1001
references.pmid: 6101994
references.citation: Cell Cycle. 2008 Apr 1;7(7):853-8
references.pmid: 18414050
references.citation: Histopathology. 2013 Aug;63(2):225-33
references.pmid: 23738752
references.citation: PLoS One. 2012;7(6):e40127
references.pmid: 22768238
references.citation: PLoS Genet. 2007 Mar 16;3(3):e42
references.pmid: 17367212
references.citation: Cancer Invest. 1997;15(1):8-17
references.pmid: 9028385
references.citation: Carcinogenesis. 2009 Jun;30(6):1003-7
references.pmid: 19380522
references.citation: Carcinogenesis. 2008 Mar;29(3):579-84
references.pmid: 18192692
references.citation: Mol Carcinog. 2014 Apr;53(4):280-5
references.pmid: 23065910
references.citation: Zhonghua Zhong Liu Za Zhi. 2012 Nov;34(11):835-7
references.pmid: 23291132
references.citation: Prostate Cancer Prostatic Dis. 2013 Dec;16(4):308-14
references.pmid: 24061634
references.citation: Blood. 2003 Nov 15;102(10):3727-36
references.pmid: 12893766
references.citation: Carcinogenesis. 2008 Jul;29(7):1306-11
references.pmid: 18477647
references.citation: Pharmacogenet Genomics. 2013 Mar;23(3):142-7
references.pmid: 23324806
references.citation: World J Gastroenterol. 2011 Feb 21;17(7):932-7
references.pmid: 21412503
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Cancer Res. 2010 Dec 1;70(23):9641-9
references.pmid: 21084273
references.citation: Cancer. 2012 Oct 1;118(19):4670-80
references.pmid: 22282400
references.citation: Endocr Relat Cancer. 2013 Nov 04;20(6):861-74
references.pmid: 24042462
references.citation: Carcinogenesis. 2011 Nov;32(11):1668-74
references.pmid: 21934093
references.citation: Cancer Epidemiol Biomarkers Prev. 2001 Aug;10(8):823-9
references.pmid: 11489748
references.citation: Carcinogenesis. 2009 Jan;30(1):59-64
references.pmid: 19028706
references.citation: BMC Cancer. 2012 Nov 20;12:534
references.pmid: 23167843
references.citation: BMC Cancer. 2010 Mar 10;10:89
references.pmid: 20219106
references.citation: PLoS One. 2013 Aug 16;8(8):e72197
references.pmid: 23977251
references.citation: Clin Cancer Res. 2011 Dec 15;17(24):7723-31
references.pmid: 21994416
references.citation: Nat Genet. 2006 Dec;38(12):1452-6
references.pmid: 17072316
references.citation: Clin Cancer Res. 2006 Dec 15;12(24):7347-52
references.pmid: 17189406
references.citation: Carcinogenesis. 2012 Jul;33(7):1346-51
references.pmid: 22581836
references.citation: Curr Biol. 2001 Oct 16;11(20):1600-5
references.pmid: 11676921
references.citation: Clin Cancer Res. 2010 Jul 15;16(14):3713-20
references.pmid: 20501619
references.citation: Fam Cancer. 2006;5(1):89-93
references.pmid: 16528612
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10737-42
references.pmid: 20498076
references.citation: PLoS One. 2013 May 28;8(5):e64973
references.pmid: 23724109
references.citation: Carcinogenesis. 2008 Jul;29(7):1394-9
references.pmid: 18550570
references.citation: Carcinogenesis. 2012 Dec;33(12):2377-83
references.pmid: 22971574
references.citation: Carcinogenesis. 2009 Dec;30(12):2064-9
references.pmid: 19917630
references.citation: CA Cancer J Clin. 2005 Jan-Feb;55(1):45-54; quiz 57
references.pmid: 15661686
references.citation: BMJ. 2000 Sep 9;321(7261):624-8
references.pmid: 10977847
references.citation: Cancer Res. 2010 Aug 15;70(16):6509-15
references.pmid: 20647319
references.citation: Can J Urol. 2011 Oct;18(5):5875-83
references.pmid: 22018148
references.citation: Cancer Epidemiol Biomarkers Prev. 2013 Mar;22(3):461-6
references.pmid: 23307532
references.citation: Nat Rev Mol Cell Biol. 2006 Feb;7(2):85-96
references.pmid: 16493415
references.citation: Gene. 2012 Oct 1;507(1):95-8
references.pmid: 22824466
references.citation: Cancer Res. 2010 Apr 1;70(7):2789-98
references.pmid: 20332227
references.citation: Nat Immunol. 2004 Nov;5(11):1134-42
references.pmid: 15467723
references.citation: Am J Cancer Res. 2012;2(3):298-308
references.pmid: 22679560
references.citation: Cancer Res. 2010 Jan 1;70(1):36-45
references.pmid: 20028859
references.citation: J Immunol. 1992 May 15;148(10):3302-12
references.pmid: 1374453
references.citation: Clin Cancer Res. 2006 Dec 1;12(23):7194-201
references.pmid: 17145846
references.citation: Anticancer Res. 2008 May-Jun;28(3A):1525-9
references.pmid: 18630507
references.citation: Nat Rev Genet. 2008 Feb;9(2):102-14
references.pmid: 18197166
references.citation: J Clin Oncol. 2004 Jul 1;22(13):2594-601
references.pmid: 15173214
references.citation: PLoS One. 2011;6(7):e22509
references.pmid: 21799879
references.citation: Gastroenterology. 2010 Jun;138(6):2101-2114.e5
references.pmid: 20420949
references.citation: PLoS One. 2012;7(12):e49823
references.pmid: 23239971
references.citation: PLoS One. 2010 May 19;5(5):e10714
references.pmid: 20502714
references.citation: Cell. 2003 Dec 26;115(7):787-98
references.pmid: 14697198
references.citation: Endocr Relat Cancer. 2008 Sep;15(3):657-64
references.pmid: 18524948
references.citation: Pharmacol Ther. 2013 Jan;137(1):55-63
references.pmid: 22964086
references.citation: Cancer Res. 2004 Sep 1;64(17):6214-24
references.pmid: 15342407
references.citation: Oncogene. 2013 Jan 10;32(2):242-50
references.pmid: 22349819
references.citation: Mol Cell. 2010 Oct 8;40(1):22-33
references.pmid: 20932472
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13561-2
references.pmid: 20660767
references.citation: Cancer Res. 2008 Oct 15;68(20):8535-40
references.pmid: 18922928
references.citation: Mol Cell. 2008 Feb 29;29(4):517-24
references.pmid: 18313389
references.citation: J Clin Invest. 2008 Jul;118(7):2600-8
references.pmid: 18521189
references.citation: Mutagenesis. 2013 Jan;28(1):49-55
references.pmid: 23028094
references.citation: Int J Oncol. 2011 Apr;38(4):1153-61
references.pmid: 21318219
references.citation: PLoS One. 2013 May 28;8(5):e64331
references.pmid: 23724042
references.citation: Cell Death Dis. 2012 Nov 15;3:e423
references.pmid: 23152059
references.citation: Biochemistry. 1996 Jun 18;35(24):8035-44
references.pmid: 8672508
references.citation: Cell. 1982 Nov;31(1):11-24
references.pmid: 6186379
references.citation: Nat Rev Cancer. 2010 Jun;10(6):389-402
references.pmid: 20495573
references.citation: Int J Colorectal Dis. 2004 Jan;19(1):23-42
references.pmid: 12827409
references.citation: Lung Cancer. 2010 Jul;69(1):51-3
references.pmid: 19854534
references.citation: Cancer Res. 2010 Dec 1;70(23):9765-76
references.pmid: 21118967
references.citation: J Clin Oncol. 2008 Jan 20;26(3):374-9
references.pmid: 18202412
references.citation: Histochem Cell Biol. 2008 Jun;129(6):705-33
references.pmid: 18461349
references.citation: Breast Cancer Res Treat. 2008 Jul;110(1):1-7
references.pmid: 17674189
references.citation: Pharmacogenomics. 2009 Mar;10(3):399-416
references.pmid: 19290790
references.citation: J Gastroenterol. 2009;44 Suppl 19:96-101
references.pmid: 19148801
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13513-8
references.pmid: 17686970
references.citation: Clin Cancer Res. 2013 Nov 1;19(21):6044-56
references.pmid: 24036853
references.citation: Carcinogenesis. 2010 Dec;31(12):2118-23
references.pmid: 20819778
references.citation: World J Gastroenterol. 2012 Jan 28;18(4):383-7
references.pmid: 22294845
references.citation: Blood. 1994 Dec 1;84(11):3637-47
references.pmid: 7949119
references.citation: Nat Rev Cancer. 2005 Nov;5(11):845-56
references.pmid: 16239904
references.citation: Nat Genet. 2006 Jul;38(7):813-8
references.pmid: 16751773
references.citation: J Natl Cancer Inst. 2002 May 1;94(9):681-90
references.pmid: 11983757
references.citation: Mol Cancer Res. 2012 Jan;10(1):86-95
references.pmid: 22064658
references.citation: Mol Cell. 2007 Aug 17;27(4):636-46
references.pmid: 17707234
references.citation: Cancer Res. 2011 Aug 1;71(15):5175-81
references.pmid: 21676885
references.citation: Int J Cancer. 2012 Sep 15;131(6):1318-22
references.pmid: 22095217
references.citation: Carcinogenesis. 2013 Mar;34(3):689-93
references.pmid: 23188672
references.citation: Int J Cancer. 2010 Dec 1;127(11):2520-9
references.pmid: 20162574
references.citation: Clin Cancer Res. 2011 Jun 1;17(11):3742-50
references.pmid: 21385923
references.citation: Front Biosci (Landmark Ed). 2011 Jan 01;16(3):1144-56
references.pmid: 21196223
references.citation: Neoplasia. 2011 Oct;13(10):961-70
references.pmid: 22028621
references.citation: Cancer Res. 2012 Jul 1;72(13):3217-27
references.pmid: 22556262
references.citation: J Virol. 2012 Feb;86(3):1544-54
references.pmid: 22114332
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Jun;18(6):1869-80
references.pmid: 19505920
references.citation: EMBO J. 1990 May;9(5):1495-502
references.pmid: 2184032
references.citation: Ann N Y Acad Sci. 1995 Sep 30;768:91-100
references.pmid: 8526389
references.citation: Cell Mol Life Sci. 2009 Mar;66(5):788-99
references.pmid: 18979208
references.citation: BMC Cancer. 2011 Feb 22;11:80
references.pmid: 21338529
references.citation: Cancer Epidemiol Biomarkers Prev. 2003 Jun;12(6):527-33
references.pmid: 12814998
references.citation: J Natl Cancer Inst. 2007 Apr 4;99(7):558-68
references.pmid: 17406000
references.citation: J Natl Cancer Inst. 1999 Jan 20;91(2):176-81
references.pmid: 9923860