title: MicroRNA-196a is a putative diagnostic biomarker and therapeutic target for laryngeal cancer.
abstract: BACKGROUND
  MicroRNA (miRNA) is an emerging subclass of small non-coding RNAs that regulates gene expression and has a pivotal role for many physiological processes including cancer development. Recent reports revealed the role of miRNAs as ideal biomarkers and therapeutic targets due to their tissue- or disease-specific nature. Head and neck cancer (HNC) is a major cause of cancer-related mortality and morbidity, and laryngeal cancer has the highest incidence in it. However, the molecular mechanisms involved in laryngeal cancer development remain to be known and highly sensitive biomarkers and novel promising therapy is necessary.
  
  
  RESULTS
  To explore laryngeal cancer-specific miRNAs, RNA from 5 laryngeal surgical specimens including cancer and non-cancer tissues were hybridized to microarray carrying 723 human miRNAs. The resultant differentially expressed miRNAs were further tested by using quantitative real time PCR (qRT-PCR) on 43 laryngeal tissue samples including cancers, noncancerous counterparts, benign diseases and precancerous dysplasias. Significant expressional differences between matched pairs were reproduced in miR-133b, miR-455-5p, and miR-196a, among which miR-196a being the most promising cancer biomarker as validated by qRT-PCR analyses on additional 84 tissue samples. Deep sequencing analysis revealed both quantitative and qualitative deviation of miR-196a isomiR expression in laryngeal cancer. In situ hybridization confirmed laryngeal cancer-specific expression of miR-196a in both cancer and cancer stroma cells. Finally, inhibition of miR-196a counteracted cancer cell proliferation in both laryngeal cancer-derived cells and mouse xenograft model.
  
  
  CONCLUSIONS
  Our study provided the possibilities that miR-196a might be very useful in diagnosing and treating laryngeal cancer.
authors: Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan.
authors: Koichiro
authors: K
authors: Saito
authors: Koji
authors: K
authors: Inagaki
authors: Takahiro
authors: T
authors: Kamimoto
authors: Yoko
authors: Y
authors: Ito
authors: Toshiaki
authors: T
authors: Sugita
authors: Satoko
authors: S
authors: Nakajo
authors: Akira
authors: A
authors: Hirasawa
authors: Arifumi
authors: A
authors: Iwamaru
authors: Takashi
authors: T
authors: Ishikura
authors: Hideki
authors: H
authors: Hanaoka
authors: Keisuke
authors: K
authors: Okubo
authors: Tokio
authors: T
authors: Onozaki
authors: Takeru
authors: T
authors: Zama
mesh_terms: D000368:Aged; D000818:Animals; D001692:Biological Transport; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007822:Laryngeal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C542543:MIRN196 microRNA, human; D035683:MicroRNAs
references: Nature. 2005 Feb 17;433(7027):769-73
references: 15685193
references: Cancer Res. 2005 Aug 15;65(16):7065-70
references: 16103053
references: AAPS J. 2009 Dec;11(4):747-57
references: 19876744
references: Lab Invest. 2009 May;89(5):597-606
references: 19290006
references: Med Hypotheses. 2006;66(3):612-35
references: 16359827
references: FASEB J. 2009 Mar;23(3):806-12
references: 18952709
references: Annu Rev Genomics Hum Genet. 2007;8:215-39
references: 17506656
references: Hepatology. 2009 May;49(5):1571-82
references: 19296470
references: Genome Res. 2009 Jan;19(1):92-105
references: 18955434
references: Dev Biol. 2007 Feb 1;302(1):1-12
references: 16989803
references: Int J Cancer. 2009 Jul 15;125(2):345-52
references: 19378336
references: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2999-3004
references: 14973191
references: DNA Cell Biol. 2007 May;26(5):311-20
references: 17504027
references: DNA Cell Biol. 2007 May;26(5):273-82
references: 17504023
references: Cancer Cell. 2007 Nov;12(5):414-8
references: 17996645
references: Nat Rev Genet. 2008 Nov;9(11):831-42
references: 18852696
references: RNA. 2007 May;13(5):723-30
references: 17400817
references: Cancer Res. 2009 Feb 15;69(4):1279-83
references: 19190326
references: Cancer Res. 2007 Dec 15;67(24):11612-20
references: 18089790
references: Cancer Cell. 2006 Mar;9(3):189-98
references: 16530703
references: Expert Opin Ther Targets. 2009 Dec;13(12):1439-48
references: 19839716
references: Oncogene. 2008 Nov 6;27(52):6667-78
references: 18663355
references: Br J Cancer. 2009 Aug 18;101(4):699-706
references: 19638978
references: Mol Cancer. 2006 Jul 19;5:29
references: 16854228
references: PLoS Genet. 2010 Mar 12;6(3):e1000879
references: 20300657
references: Nat Biotechnol. 2001 Apr;19(4):342-7
references: 11283592
references: Science. 2004 Apr 23;304(5670):594-6
references: 15105502
references: Cancer Res. 2007 Sep 15;67(18):8699-707
references: 17875710
references: Nat Rev Mol Cell Biol. 2005 May;6(5):376-85
references: 15852042
references: Genome Res. 2008 Apr;18(4):610-21
references: 18285502
references: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2257-61
references: 16461460
references: Nat Rev Cancer. 2006 Apr;6(4):259-69
references: 16557279
references: Oncogene. 2008 Mar 13;27(12):1788-93
references: 17891175
references: Ann Otol Rhinol Laryngol. 2008 Jan;117(1):74-9
references: 18254375
references: Clin Cancer Res. 2005 Feb 1;11(3):1044-9
references: 15709170
references: Int J Cancer. 2005 May 1;114(5):806-16
references: 15609302
references: Cancer Sci. 2007 Nov;98(11):1803-8
references: 17784873
references: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15472-7
references: 17875987
references: PLoS One. 2010 Jan 21;5(1):e8836
references: 20098684
references: World J Gastroenterol. 2009 May 7;15(17):2089-96
references: 19418581
references: Int J Cancer. 2010 Dec 15;127(12):2804-14
references: 21351259
references: Curr Opin Genet Dev. 2006 Feb;16(1):4-9
references: 16361094
references: Circulation. 2012 Apr 10;125(14):1765-73, S1-7
references: 22403243
references: Genes Chromosomes Cancer. 2009 Jul;48(7):615-23
references: 19396864
references: Clin Cancer Res. 2003 Oct 15;9(13):4811-8
references: 14581352
references: Gynecol Oncol. 2008 Jul;110(1):13-21
references: 18589210
references: Oncology. 2009;77(1):12-21
references: 19439999
references: Nat Cell Biol. 2007 Jun;9(6):654-9
references: 17486113
references: Nat Biotechnol. 2008 Apr;26(4):462-9
references: 18362881
references: Int J Cancer. 2008 Dec 15;123(12):2791-7
references: 18798260
references: CA Cancer J Clin. 2002 Jan-Feb;52(1):23-47
references: 11814064
references: Oncogene. 2007 Jun 28;26(30):4442-52
references: 17237814
references: Br J Cancer. 2009 Mar 24;100(6):1002-11
references: 19293812
references: Nature. 2005 Jun 9;435(7043):834-8
references: 15944708
references: Cancer Sci. 2007 Dec;98(12):1914-20
references: 17892514
references: Cell. 2007 Jun 29;129(7):1401-14
references: 17604727
references: J Bone Miner Res. 2009 May;24(5):816-25
references: 19063684
references: Clin Cancer Res. 2009 Feb 15;15(4):1177-83
references: 19228723
references: Nat Rev Genet. 2008 Feb;9(2):102-14
references: 18197166
references: BMC Biotechnol. 2007 Jun 29;7:36
references: 17603869
references: RNA. 2007 Jan;13(1):151-9
references: 17105992
references: PLoS One. 2008;3(12):e4029
references: 19107213
references: Clin Cancer Res. 2009 Mar 15;15(6):1915-22
references: 19276261
references: J Cell Physiol. 2007 Feb;210(2):279-89
references: 17096367
references: Biochemistry (Mosc). 2007 May;72(5):578-82
references: 17573714
references: Oncol Rep. 2007 Apr;17(4):753-60
references: 17342311
references: Clin Cancer Res. 2006 Jan 15;12(2):405-10
references: 16428479
references: Trends Mol Med. 2006 Dec;12(12):580-7
references: 17071139
references: Leuk Res. 2011 Feb;35(2):208-13
references: 20570349
references: Sci Signal. 2009 Jan 06;2(52):pe1
references: 19126861
references: J Biol Chem. 1992 Aug 5;267(22):16000-6
references: 1639825
references: Cell. 2004 Jan 23;116(2):281-97
references: 14744438
references: Cancer Sci. 2010 Jan;101(1):241-9
references: 19891660
references: Nat Rev Cancer. 2006 Nov;6(11):857-66
references: 17060945
references: Head Neck. 2013 May;35(5):720-8
references: 22605671
references: Curr Med Chem. 2007;14(9):969-85
references: 17439397
references: Brain Pathol. 2008 Jan;18(1):113-21
references: 18226106
references: J Biol Chem. 2009 Aug 21;284(34):23094-106
references: 19546220
references: Clin Cancer Res. 2008 May 1;14(9):2588-92
references: 18451220
references: CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66
references: 17237035
references: PLoS One. 2012;7(12):e52568
references: 23285092