title: MicroRNAome genome: a treasure for cancer diagnosis and therapy.
abstract: The interplay between abnormalities in genes coding for proteins and noncoding microRNAs (miRNAs) has been among the most exciting yet unexpected discoveries in oncology over the last decade. The complexity of this network has redefined cancer research as miRNAs, produced from what was once considered "genomic trash," have shown to be crucial for cancer initiation, progression, and dissemination. Naturally occurring miRNAs are very short transcripts that never produce a protein or amino acid chain, but act by regulating protein expression during cellular processes such as growth, development, and differentiation at the transcriptional, posttranscriptional, and/or translational level. In this review article, miRNAs are presented as ubiquitous players involved in all cancer hallmarks. The authors also describe the most used methods to detect their expression, which have revealed the identity of hundreds of miRNAs dysregulated in cancer cells or tumor microenvironment cells. Furthermore, the role of miRNAs as hormones and as reliable cancer biomarkers and predictors of treatment response is discussed. Along with this, the authors explore current strategies in designing miRNA-targeting therapeutics, as well as the associated challenges that research envisions to overcome. Finally, a new wave in molecular oncology translational research is introduced: the study of long noncoding RNAs.
authors.affiliation: Department of Functional Genomics, The Oncology Institute, Research Center for Functional Genomics, Biomedicine and Translational Medicine, Department of Immunology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Berindan-Neagoe
authors.forename: Paloma del C
authors.initials: Pdel C
authors.lastname: Monroig
authors.forename: Barbara
authors.initials: B
authors.lastname: Pasculli
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology* / Q000627:therapeutic use; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: cancer.; diagnosis; microRNA; therapy
references.citation: Hepatogastroenterology. 2013 Oct;60(127):1809-13
references.pmid: 24624454
references.citation: Nat Struct Mol Biol. 2006 Dec;13(12):1097-101
references.pmid: 17099701
references.citation: Crit Rev Oncog. 2013;18(4):327-40
references.pmid: 23614619
references.citation: Nat Rev Drug Discov. 2013 Jun;12(6):433-46
references.pmid: 23722346
references.citation: Nature. 2007 Oct 11;449(7163):682-8
references.pmid: 17898713
references.citation: Expert Rev Mol Diagn. 2014 Apr;14(3):347-63
references.pmid: 24649821
references.citation: Semin Oncol. 2006 Apr;33(2):167-73
references.pmid: 16616063
references.citation: Mol Cell. 2011 Sep 16;43(6):904-14
references.pmid: 21925379
references.citation: Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6573-8
references.pmid: 21460253
references.citation: Cell. 2012 May 11;149(4):819-31
references.pmid: 22541069
references.citation: Int J Cancer. 2013 Jan 1;132(1):116-27
references.pmid: 22674182
references.citation: Nat Rev Drug Discov. 2010 Oct;9(10):775-89
references.pmid: 20885409
references.citation: Int J Biochem Cell Biol. 2012 Sep;44(9):1448-56
references.pmid: 22634383
references.citation: Cold Spring Harb Perspect Med. 2014 Apr 15;4(8):
references.pmid: 24737842
references.citation: Eur J Immunol. 2014 Jul;44(7):2085-95
references.pmid: 24723426
references.citation: Blood. 2013 Sep 12;122(11):1891-9
references.pmid: 23821659
references.citation: Prostate. 2011 Feb 15;71(3):326-31
references.pmid: 20842666
references.citation: Nat Med. 2008 Jul;14(7):723-30
references.pmid: 18587408
references.citation: Cancer Cell. 2013 Feb 11;23(2):186-99
references.pmid: 23410973
references.citation: Int J Mol Sci. 2013 Oct 09;14(10):19987-20018
references.pmid: 24113581
references.citation: Br J Haematol. 2013 Oct;163(1):93-103
references.pmid: 23888996
references.citation: Cell. 2006 Mar 24;124(6):1169-81
references.pmid: 16564011
references.citation: Leukemia. 2013 Feb;27(2):353-61
references.pmid: 22810507
references.citation: Nat Rev Clin Oncol. 2014 Mar;11(3):145-56
references.pmid: 24492836
references.citation: PLoS One. 2013 Oct 21;8(10):e78115
references.pmid: 24205116
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: Mod Pathol. 2010 Jun;23(6):814-23
references.pmid: 20348879
references.citation: Nat Rev Cancer. 2009 Apr;9(4):293-302
references.pmid: 19262572
references.citation: Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):522-7
references.pmid: 21187425
references.citation: BMC Bioinformatics. 2014 Jan 28;15:29
references.pmid: 24472427
references.citation: Br J Cancer. 2014 Apr 29;110(9):2291-9
references.pmid: 24595006
references.citation: Leukemia. 2014 Apr;28(4):804-12
references.pmid: 24072101
references.citation: Curr Opin Pharmacol. 2010 Oct;10(5):543-50
references.pmid: 20541466
references.citation: Science. 2007 Mar 16;315(5818):1576-9
references.pmid: 17322030
references.citation: Clin Cancer Res. 2012 Aug 15;18(16):4234-9
references.pmid: 22711704
references.citation: Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1002-7
references.pmid: 24371310
references.citation: Oncogene. 2012 Mar 29;31(13):1609-22
references.pmid: 21860412
references.citation: Int J Cancer. 2010 Jul 1;127(1):118-26
references.pmid: 19876917
references.citation: Cell Death Dis. 2014 Apr 24;5:e1197
references.pmid: 24763054
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2999-3004
references.pmid: 14973191
references.citation: Clin Sci (Lond). 2011 Aug;121(4):141-58
references.pmid: 21526983
references.citation: Nat Med. 2008 Oct;14(10):1036-40
references.pmid: 18841144
references.citation: Mol Cancer. 2013 Jun 10;12:57
references.pmid: 23758919
references.citation: J Biol Chem. 2012 Jan 6;287(2):1397-405
references.pmid: 22123823
references.citation: Cancer Cell. 2012 Mar 20;21(3):297-308
references.pmid: 22439925
references.citation: Nat Biotechnol. 2010 Apr;28(4):341-7
references.pmid: 20351690
references.citation: Cancer Cell. 2007 Sep;12(3):215-29
references.pmid: 17785203
references.citation: Nucleic Acids Res. 2013 Dec;41(22):e203
references.pmid: 24194606
references.citation: Nat Rev Genet. 2012 Apr 18;13(5):358-69
references.pmid: 22510765
references.citation: Nature. 2008 Oct 23;455(7216):1124-8
references.pmid: 18806776
references.citation: Cancer Res. 2013 Jul 1;73(13):3913-26
references.pmid: 23636127
references.citation: Cancer J. 2012 May-Jun;18(3):268-74
references.pmid: 22647364
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1608-13
references.pmid: 18227514
references.citation: Leuk Lymphoma. 2013 Jan;54(1):189-91
references.pmid: 22712836
references.citation: J Cell Biol. 2012 Oct 29;199(3):407-12
references.pmid: 23109665
references.citation: Lancet Oncol. 2011 Mar;12(3):273-85
references.pmid: 21345725
references.citation: J Biol Chem. 2008 Jun 6;283(23):15878-83
references.pmid: 18417479
references.citation: Leuk Res. 2012 Mar;36(3):293-8
references.pmid: 22099053
references.citation: Cell. 2013 Feb 14;152(4):844-58
references.pmid: 23415231
references.citation: Cancer Res. 2011 May 1;71(9):3387-99
references.pmid: 21385897
references.citation: Cell. 2005 Mar 11;120(5):635-47
references.pmid: 15766527
references.citation: Cancer Cell. 2008 Mar;13(3):272-86
references.pmid: 18328430
references.citation: J Pathol. 2011 Sep;225(1):43-53
references.pmid: 21630269
references.citation: Methods. 2010 Apr;50(4):244-9
references.pmid: 20109550
references.citation: Blood. 2009 Nov 26;114(23):4761-70
references.pmid: 19745066
references.citation: Anal Chim Acta. 2011 Aug 12;699(2):134-52
references.pmid: 21704768
references.citation: Hepatology. 2012 Feb;55(2):465-75
references.pmid: 21953056
references.citation: Nat Rev Clin Oncol. 2011 Jun 07;8(8):467-77
references.pmid: 21647195
references.citation: Technol Cancer Res Treat. 2010 Apr;9(2):123-38
references.pmid: 20218735
references.citation: Science. 2007 Jan 5;315(5808):97-100
references.pmid: 17204650
references.citation: PLoS One. 2012;7(5):e38129
references.pmid: 22662276
references.citation: Nat Rev Cancer. 2006 Apr;6(4):259-69
references.pmid: 16557279
references.citation: Mol Cell. 2007 Jun 8;26(5):745-52
references.pmid: 17540599
references.citation: Gastroenterology. 2012 Jul;143(1):35-47.e2
references.pmid: 22580099
references.citation: Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7413-7
references.pmid: 23589849
references.citation: J Clin Oncol. 2013 Jun 10;31(17):2086-93
references.pmid: 23650424
references.citation: Mol Cell Biol. 2007 Mar;27(5):1859-67
references.pmid: 17194750
references.citation: Clin Cancer Res. 2010 Jan 15;16(2):430-41
references.pmid: 20068076
references.citation: Oncologist. 2012;17(6):801-12
references.pmid: 22618571
references.citation: Clin Gastroenterol Hepatol. 2013 Jun;11(6):681-8.e3
references.pmid: 23267864
references.citation: Cell. 2010 Mar 5;140(5):652-65
references.pmid: 20211135
references.citation: J Surg Oncol. 2013 Jun;107(7):767-71
references.pmid: 23609137
references.citation: Hepatology. 2012 Sep;56(3):1025-33
references.pmid: 22473819
references.citation: Cell Cycle. 2008 Mar 15;7(6):759-64
references.pmid: 18344688
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14879-84
references.pmid: 18812516
references.citation: N Engl J Med. 2005 Oct 27;353(17):1793-801
references.pmid: 16251535
references.citation: Nat Methods. 2006 Jan;3(1):27-9
references.pmid: 16369549
references.citation: PLoS One. 2014 Feb 20;9(2):e89223
references.pmid: 24586608
references.citation: J Biol Chem. 2012 Jun 29;287(27):23227-35
references.pmid: 22593586
references.citation: Br J Cancer. 2013 Sep 17;109(6):1625-35
references.pmid: 23969726
references.citation: Cell. 2012 Mar 16;148(6):1172-87
references.pmid: 22424228
references.citation: Invest Ophthalmol Vis Sci. 2014 Feb 18;55(2):941-51
references.pmid: 24436191
references.citation: Curr Opin Cell Biol. 2009 Jun;21(3):470-9
references.pmid: 19411171
references.citation: Clin Cancer Res. 2014 Dec 15;20(24):6247-53
references.pmid: 25512634
references.citation: Mol Cell. 2014 Feb 6;53(3):393-406
references.pmid: 24507715
references.citation: Mol Ther Nucleic Acids. 2013 Apr 16;2:e84
references.pmid: 23591808
references.citation: Endocr Relat Cancer. 2010 Dec 21;18(1):85-95
references.pmid: 21051560
references.citation: Ann Surg. 2013 Sep;258(3):400-8
references.pmid: 24022433
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2110-6
references.pmid: 22753494
references.citation: Oncogene. 2007 Jul 26;26(34):5017-22
references.pmid: 17297439
references.citation: Int J Nanomedicine. 2013;8:61-71
references.pmid: 23293520
references.citation: Front Oncol. 2013 Jun 13;3:153
references.pmid: 23785667
references.citation: PLoS One. 2013 Nov 01;8(11):e77853
references.pmid: 24223734
references.citation: Cell. 2009 May 1;137(3):586-586.e1
references.pmid: 19410551
references.citation: PLoS One. 2011 Mar 17;6(3):e17745
references.pmid: 21445232
references.citation: J Biol Chem. 2007 Jan 26;282(4):2135-43
references.pmid: 17135249
references.citation: JAMA. 2011 Jan 5;305(1):59-67
references.pmid: 21205967
references.citation: Mol Oncol. 2014 Jul;8(5):874-83
references.pmid: 24694649
references.citation: Neuro Oncol. 2014 Apr;16(4):520-7
references.pmid: 24435880
references.citation: Neuro Oncol. 2012 Jun;14(6):689-700
references.pmid: 22492962
references.citation: Nat Rev Drug Discov. 2013 Nov;12(11):847-65
references.pmid: 24172333
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9667-72
references.pmid: 17535905
references.citation: J Biol Chem. 2013 Nov 29;288(48):34343-51
references.pmid: 24133215
references.citation: Nature. 2012 Feb 15;482(7385):347-55
references.pmid: 22337054
references.citation: J Mol Med (Berl). 2013 Apr;91(4):431-7
references.pmid: 23519402
references.citation: Histol Histopathol. 2013 Apr;28(4):437-51
references.pmid: 23224781
references.citation: Nature. 2005 Jun 9;435(7043):839-43
references.pmid: 15944709
references.citation: Blood. 2007 Jun 15;109(12):5079-86
references.pmid: 17351108
references.citation: Gynecol Oncol. 2010 Jul;118(1):88-92
references.pmid: 20439111
references.citation: Gastric Cancer. 2015 Apr;18(2):271-9
references.pmid: 24626859
references.citation: Cell. 2003 Jun 13;113(6):673-6
references.pmid: 12809598
references.citation: Diabetes Obes Metab. 2012 Oct;14 Suppl 3:12-21
references.pmid: 22928560
references.citation: Mol Cancer. 2011 Sep 22;10:117
references.pmid: 21939504
references.citation: Nat Biotechnol. 2008 Apr;26(4):462-9
references.pmid: 18362881
references.citation: Curr Biol. 2007 Aug 7;17(15):1298-307
references.pmid: 17656095
references.citation: Science. 2013 Aug 16;341(6147):789-92
references.pmid: 23907535
references.citation: Mol Cancer Ther. 2007 May;6(5):1483-91
references.pmid: 17483436
references.citation: J Clin Oncol. 2014 Mar 10;32(8):768-73
references.pmid: 24419137
references.citation: Clin Cancer Res. 2013 Aug 15;19(16):4477-87
references.pmid: 23797906
references.citation: J Surg Oncol. 2007 Dec 15;96(8):693-703
references.pmid: 18081153
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3713-8
references.pmid: 21300873
references.citation: Annu Rev Biochem. 2012;81:145-66
references.pmid: 22663078
references.citation: Cell. 2011 Aug 5;146(3):353-8
references.pmid: 21802130
references.citation: Genes Chromosomes Cancer. 2014 Sep;53(9):713-24
references.pmid: 24764226
references.citation: Nature. 2005 Jun 9;435(7043):834-8
references.pmid: 15944708
references.citation: Mutat Res. 2011 Dec 1;717(1-2):85-90
references.pmid: 21402084
references.citation: J Clin Invest. 2010 Apr;120(4):1298-309
references.pmid: 20237410
references.citation: Clin Cancer Res. 2013 Oct 1;19(19):5423-33
references.pmid: 23946296
references.citation: PLoS One. 2014 Apr 04;9(4):e92921
references.pmid: 24705249
references.citation: FEBS Lett. 2014 Jan 3;588(1):99-104
references.pmid: 24269686
references.citation: Cancer Cell. 2010 Jan 19;17(1):28-40
references.pmid: 20060366
references.citation: Expert Rev Mol Diagn. 2013 Mar;13(2):183-204
references.pmid: 23477558
references.citation: Cancer Res. 2013 Aug 1;73(15):4801-9
references.pmid: 23774211
references.citation: Cancer Genet Cytogenet. 2010 Jul 15;200(2):154-60
references.pmid: 20620599
references.citation: Gut. 2012 Oct;61(10):1447-53
references.pmid: 22052060
references.citation: J Gastroenterol Hepatol. 2010 Oct;25(10):1674-80
references.pmid: 20880178
references.citation: Stroke. 2012 Oct;43(10):2800-2
references.pmid: 22949471
references.citation: Prog Hematol. 1964;4:187-202
references.pmid: 14272796
references.citation: Anticancer Res. 2014 Feb;34(2):665-9
references.pmid: 24510997
references.citation: Clin Cancer Res. 2011 Apr 1;17(7):1875-82
references.pmid: 21350005
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15524-9
references.pmid: 12434020
references.citation: Cancer Biol Med. 2013 Sep;10(3):123-30
references.pmid: 24379986
references.citation: Haematologica. 2014 Mar;99(3):511-8
references.pmid: 24241494
references.citation: Genes Dev. 2007 May 1;21(9):1025-30
references.pmid: 17437991
references.citation: J Biol Chem. 2013 Apr 12;288(15):10849-59
references.pmid: 23439645
references.citation: Front Genet. 2013 Jan 09;3:308
references.pmid: 23316211
references.citation: JAMA. 2008 Jan 30;299(4):425-36
references.pmid: 18230780
references.citation: Mol Carcinog. 2011 Feb;50(2):136-42
references.pmid: 21229610
references.citation: Nat Rev Cancer. 2011 May;11(5):325-37
references.pmid: 21508971
references.citation: Expert Opin Drug Metab Toxicol. 2011 Jun;7(6):765-74
references.pmid: 21521129
references.citation: Br J Haematol. 2013 Aug;162(3):348-59
references.pmid: 23718138
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Nat Med. 2008 Nov;14(11):1271-7
references.pmid: 18931683
references.citation: Semin Cancer Biol. 2014 Aug;27:46-51
references.pmid: 24607282
references.citation: Science. 2007 Dec 21;318(5858):1931-4
references.pmid: 18048652
references.citation: Front Genet. 2012 Jul 02;3:120
references.pmid: 22783274
references.citation: Cell Death Differ. 2008 Apr;15(4):667-71
references.pmid: 18219318
references.citation: Oncotarget. 2014 Mar 15;5(5):1174-84
references.pmid: 24632568
references.citation: Blood. 2012 Apr 12;119(15):3503-11
references.pmid: 22343918
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19971-6
references.pmid: 18056805
references.citation: BMC Cancer. 2010 Apr 29;10:173
references.pmid: 20429937
references.citation: Hum Mol Genet. 2006 Apr 15;15 Spec No 1:R17-29
references.pmid: 16651366
references.citation: Anticancer Res. 2014 Feb;34(2):557-64
references.pmid: 24510984
references.citation: Nature. 2007 Jun 28;447(7148):1130-4
references.pmid: 17554337
references.citation: Cancer Discov. 2013 Nov;3(11):1302-15
references.pmid: 24002999
references.citation: Mol Psychiatry. 2014 Apr;19(4):486-94
references.pmid: 23628989
references.citation: BMC Cancer. 2012 Mar 08;12:83
references.pmid: 22397399
references.citation: Nat Neurosci. 2012 Jun;15(6):827-35
references.pmid: 22610069
references.citation: J Clin Oncol. 2010 Apr 1;28(10):1721-6
references.pmid: 20194856
references.citation: N Engl J Med. 2013 May 2;368(18):1685-94
references.pmid: 23534542
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5166-71
references.pmid: 18362358
references.citation: RNA. 2008 May;14(5):844-52
references.pmid: 18375788
references.citation: Methods Mol Biol. 2013;980:43-59
references.pmid: 23359149
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: Neuro Oncol. 2012 Jan;14(1):29-33
references.pmid: 21937590
references.citation: Clin Cancer Res. 2010 Aug 15;16(16):4246-55
references.pmid: 20682703
references.citation: Nat Rev Cancer. 2006 Nov;6(11):857-66
references.pmid: 17060945
references.citation: J Immunol. 2013 Dec 15;191(12):6250-60
references.pmid: 24227773
references.citation: PLoS One. 2013;8(2):e56718
references.pmid: 23437222
references.citation: Nat Protoc. 2008;3(4):563-78
references.pmid: 18388938
references.citation: Nature. 2010 Sep 2;467(7311):86-90
references.pmid: 20693987
references.citation: Blood. 2010 Aug 12;116(6):945-52
references.pmid: 20393129
references.citation: Oncogene. 2008 Sep 4;27(39):5204-13
references.pmid: 18504438
references.citation: Nature. 2009 Apr 9;458(7239):762-5
references.pmid: 19219026
references.citation: J Cancer Res Clin Oncol. 2012 Oct;138(10):1659-66
references.pmid: 22638884
references.citation: Proc Natl Acad Sci U S A. 2006 May 2;103(18):7024-9
references.pmid: 16641092
references.citation: Circ Res. 2012 Oct 26;111(10):1349-62
references.pmid: 23104877
references.citation: Nat Rev Cancer. 2011 Aug 05;11(9):644-56
references.pmid: 21822212
references.citation: Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9845-50
references.pmid: 23697367
references.citation: Cancer Res. 2007 Nov 15;67(22):11001-11
references.pmid: 18006846
references.citation: Cell Metab. 2010 Oct 6;12(4):352-361
references.pmid: 20889127
references.citation: Blood. 2014 Apr 10;123(15):2412-5
references.pmid: 24596420
references.citation: Oncogene. 2012 Oct 25;31(43):4577-87
references.pmid: 22266873
references.citation: Science. 2002 Sep 20;297(5589):2056-60
references.pmid: 12154197
references.citation: Clin Chem. 2013 Oct;59(10):1489-96
references.pmid: 23748853
references.citation: Ann Surg. 2014 Apr;259(4):735-43
references.pmid: 23982750