title: Integrating the MicroRNome into the study of lung disease.
abstract: Over the last 15 years, investigators have identified small noncoding RNAs as regulators of gene expression. One type of noncoding RNAs are termed microRNAs (miRNAs). miRNAs are evolutionary conserved, approximately 22-nucleotide single-stranded RNAs that target genes by inducing mRNA degradation or by inhibiting translation. miRNAs are implicated in many critical cellular processes, including apoptosis, proliferation, and differentiation. Furthermore, it is estimated that miRNAs may be responsible for regulating the expression of nearly one-third of the human genome. Despite the identification of greater than 500 mature miRNAs, very little is known about their biological functions and functional targets. In the last 5 years, researchers have increasingly focused on the functional relevance and role that miRNAs play in the pathogenesis of human disease. miRNAs are known to be important in solid organ and hematological malignancies, heart disease, as potential modulators of the immune response, and organ development. It is anticipated that miRNA analysis will emerge as an important complement to proteomic and genomic studies to further our understanding of disease pathogenesis. Despite the application of genomics and proteomics to the study of human lung disease, few studies have examined miRNA expression. This perspective is not meant to be an exhaustive review of miRNA biology but will provide an overview of both miRNA biogenesis and our current understanding of the role of miRNAs in lung disease as well as a perspective on the importance of integrating this analysis as a tool for identifying and understanding the biological pathways in lung-disease pathogenesis.
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Ohio State University Medical Center, Columbus, OH 43210, USA. Patrick.Nana-Sinkam@osumc.edu
authors.forename: Serge P
authors.initials: SP
authors.lastname: Nana-Sinkam
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Hunter
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Schmittgen
authors.forename: Richard
authors.initials: R
authors.lastname: Gelinas
authors.forename: David
authors.initials: D
authors.lastname: Galas
authors.forename: Clay B
authors.initials: CB
authors.lastname: Marsh
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D008171:Lung Diseases / Q000378:metabolism / Q000503:physiopathology*; D035683:MicroRNAs / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs
references.citation: BMC Genomics. 2007 Jul 17;8:240
references.pmid: 17640343
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2999-3004
references.pmid: 14973191
references.citation: Oncogene. 2008 Apr 3;27(15):2128-36
references.pmid: 17968323
references.citation: Oncogene. 2007 Sep 6;26(41):6099-105
references.pmid: 17384677
references.citation: Nat Med. 2007 May;13(5):613-8
references.pmid: 17468766
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9740-4
references.pmid: 15210942
references.citation: Semin Cancer Biol. 2008 Apr;18(2):131-40
references.pmid: 18291670
references.citation: J Cell Physiol. 2007 Nov;213(2):412-9
references.pmid: 17674365
references.citation: Trends Genet. 2006 Mar;22(3):165-73
references.pmid: 16446010
references.citation: Immunity. 2007 Dec;27(6):847-59
references.pmid: 18055230
references.citation: Cell Cycle. 2006 Oct;5(19):2220-2
references.pmid: 17012846
references.citation: BMC Genomics. 2007 Jun 12;8:166
references.pmid: 17565689
references.citation: Cancer Cell. 2008 Jan;13(1):48-57
references.pmid: 18167339
references.citation: N Engl J Med. 2006 Aug 10;355(6):570-80
references.pmid: 16899777
references.citation: Cancer Res. 2005 Aug 15;65(16):7065-70
references.pmid: 16103053
references.citation: RNA. 2008 May;14(5):829-35
references.pmid: 18367718
references.citation: Mol Cell. 2007 Jul 6;27(1):91-105
references.pmid: 17612493
references.citation: Trends Biotechnol. 2008 Feb;26(2):70-6
references.pmid: 18191262
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3903-8
references.pmid: 18308936
references.citation: Cancer Cell. 2006 Mar;9(3):189-98
references.pmid: 16530703
references.citation: Nucleic Acids Res. 2006 Jan 24;34(2):e9
references.pmid: 16434699
references.citation: Nat Genet. 2007 May;39(5):673-7
references.pmid: 17401365
references.citation: Science. 2007 Apr 27;316(5824):608-11
references.pmid: 17463290
references.citation: Methods. 2007 Oct;43(2):140-5
references.pmid: 17889801
references.citation: Cell. 2005 Mar 11;120(5):635-47
references.pmid: 15766527
references.citation: Development. 2005 Nov;132(21):4645-52
references.pmid: 16224044
references.citation: Methods. 2008 Jan;44(1):47-54
references.pmid: 18158132
references.citation: Nucleic Acids Res. 2004 Feb 25;32(4):e43
references.pmid: 14985473
references.citation: Cell Res. 2008 Mar;18(3):350-9
references.pmid: 18270520
references.citation: J Biol Chem. 2007 Aug 10;282(32):23716-24
references.pmid: 17569667
references.citation: Science. 2005 Sep 2;309(5740):1577-81
references.pmid: 16141076
references.citation: Cell. 2008 Mar 7;132(5):875-86
references.pmid: 18329372
references.citation: Cancer Res. 2004 Jun 1;64(11):3753-6
references.pmid: 15172979
references.citation: Nature. 2004 Nov 11;432(7014):226-30
references.pmid: 15538371
references.citation: Mol Cell Biol. 2007 Mar;27(5):1859-67
references.pmid: 17194750
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2208-13
references.pmid: 16452165
references.citation: Cell. 1993 Dec 3;75(5):843-54
references.pmid: 8252621
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18125-30
references.pmid: 17116888
references.citation: Int J Med Sci. 2008 Apr 03;5(2):73-9
references.pmid: 18392144
references.citation: Am J Respir Crit Care Med. 2005 Dec 15;172(12):1556-62
references.pmid: 16179643
references.citation: Nature. 2007 Dec 13;450(7172):1096-9
references.pmid: 18075594
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15805-10
references.pmid: 17890317
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9667-72
references.pmid: 17535905
references.citation: Cancer Res. 2007 Aug 15;67(16):7713-22
references.pmid: 17699775
references.citation: Nucleic Acids Res. 2005 Nov 27;33(20):e179
references.pmid: 16314309
references.citation: Science. 2001 Oct 26;294(5543):858-62
references.pmid: 11679671
references.citation: Biochim Biophys Acta. 2008 Aug;1779(8):471-8
references.pmid: 18194678
references.citation: Birth Defects Res C Embryo Today. 2006 Jun;78(2):180-9
references.pmid: 16847883
references.citation: J Virol. 2008 Aug;82(16):8215-23
references.pmid: 18550664
references.citation: Oncogene. 2008 Jun 19;27(27):3845-55
references.pmid: 18246122
references.citation: BMC Genomics. 2007 Jun 15;8:172
references.pmid: 17573962
references.citation: Oncogene. 2006 Apr 20;25(17):2537-45
references.pmid: 16331254
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2746-51
references.pmid: 16477010
references.citation: Nature. 2005 Jun 9;435(7043):834-8
references.pmid: 15944708
references.citation: Cancer Res. 2005 Nov 1;65(21):9628-32
references.pmid: 16266980
references.citation: Oncogene. 2008 Jul 17;27(31):4373-9
references.pmid: 18372920
references.citation: Cell. 2005 Jan 14;120(1):15-20
references.pmid: 15652477
references.citation: RNA. 2007 Jan;13(1):151-9
references.pmid: 17105992
references.citation: Science. 2001 Feb 16;291(5507):1304-51
references.pmid: 11181995
references.citation: J Mol Biol. 2006 May 12;358(4):983-96
references.pmid: 16564540
references.citation: Dev Biol. 2007 Oct 15;310(2):442-53
references.pmid: 17765889
references.citation: Cell. 2003 Dec 26;115(7):787-98
references.pmid: 14697198
references.citation: Science. 2007 Dec 21;318(5858):1931-4
references.pmid: 18048652
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1604-9
references.pmid: 17242365
references.citation: Nature. 2004 Oct 21;431(7011):931-45
references.pmid: 15496913
references.citation: J Virol. 2008 Feb;82(4):1946-58
references.pmid: 18057241
references.citation: Cancer Res. 2005 Jul 15;65(14):6029-33
references.pmid: 16024602
references.citation: Am J Hum Genet. 2007 Oct;81(4):829-34
references.pmid: 17847008
references.citation: Nature. 2008 Apr 17;452(7189):896-9
references.pmid: 18368051
references.citation: Ann Oncol. 2008 Jun;19(6):1053-9
references.pmid: 18304967
references.citation: Cancer Res. 2007 Nov 15;67(22):11001-11
references.pmid: 18006846
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12481-6
references.pmid: 16885212