title: MicroRNA-155 expression is independently predictive of outcome in chordoma.
abstract: BACKGROUND
  Chordoma pathogenesis remains poorly understood. In this study, we aimed to evaluate the relationships between microRNA-155 (miR-155) expression and the clinicopathological features of chordoma patients, and to evaluate the functional role of miR-155 in chordoma.
  
  
  METHODS
  The miRNA expression profiles were analyzed using miRNA microarray assays. Regulatory activity of miR-155 was assessed using bioinformatic tools. miR-155 expression levels were validated by reverse transcription-polymerase chain reaction. The relationships between miR-155 expression and the clinicopathological features of chordoma patients were analyzed. Proliferative, migratory and invasive activities were assessed by MTT, wound healing, and Matrigel invasion assays, respectively.
  
  
  RESULTS
  The miRNA microarray assay revealed miR-155 to be highly expressed and biologically active in chordoma. miR-155 expression in chordoma tissues was significantly elevated, and this expression correlated significantly with disease stage (p = 0.036) and the presence of metastasis (p = 0.035). miR-155 expression also correlated significantly with poor outcomes for chordoma patients (hazard ratio, 5.32; p = 0.045). Inhibition of miR-155 expression suppressed proliferation, and the migratory and invasive activities of chordoma cells.
  
  
  CONCLUSIONS
  We have shown miR-155 expression to independently affect prognosis in chordoma. These results collectively indicate that miR-155 expression may serve not only as a prognostic marker, but also as a potential therapeutic target in chordoma.
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.|Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Osaka
authors.affiliation: Fels Institute for Cancer Research & Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Kelly
authors.affiliation: Division of Hematology/Oncology, Sarcoma Program, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Spentzos
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: Choy
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Yang
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Jacson K
authors.initials: JK
authors.lastname: Shen
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Yang
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Mankin
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hornicek
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D002817:Chordoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000556:secondary / Q000601:surgery; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008159:Lumbar Vertebrae; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012447:Sacrum; D013125:Spinal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm
keywords: RT-PCR; chordoma; miRNA microarray assay; miRNA-155 (miR-155); prognosis
references.citation: J Biomed Sci. 2013;20:79
references.pmid: 24152184
references.citation: PLoS One. 2013;8(5):e62589
references.pmid: 23667495
references.citation: PLoS One. 2011;6(4):e19137
references.pmid: 21541331
references.citation: J Bone Joint Surg Am. 2005 Oct;87(10):2211-6
references.pmid: 16203885
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
references.pmid: 9843981
references.citation: Turk Neurosurg. 2013;23(6):700-6
references.pmid: 24310451
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16170-5
references.pmid: 17911264
references.citation: Mol Med Rep. 2012 Apr;5(4):949-54
references.pmid: 22307849
references.citation: Sarcoma. 2012;2012:359739
references.pmid: 22550419
references.citation: J Cell Physiol. 2014 May;229(5):545-50
references.pmid: 24122356
references.citation: Cancer Res. 2012 Apr 1;72(7):1751-62
references.pmid: 22350414
references.citation: J Cancer Res Clin Oncol. 2006 Apr;132(4):213-8
references.pmid: 16362333
references.citation: Genes Chromosomes Cancer. 2001 Nov;32(3):203-11
references.pmid: 11579460
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: FEBS Lett. 2013 May 2;587(9):1434-9
references.pmid: 23523916
references.citation: PLoS One. 2013;8(2):e56395
references.pmid: 23437123
references.citation: Am J Pathol. 2012 Jul;181(1):26-33
references.pmid: 22609116
references.citation: Blood. 2009 Aug 13;114(7):1374-82
references.pmid: 19520806
references.citation: Proc Natl Acad Sci U S A. 2012 Dec 4;109(49):20047-52
references.pmid: 23169640
references.citation: Genome Biol. 2009;10(9):R90
references.pmid: 19723326
references.citation: Oncol Rep. 2013 Jul;30(1):17-24
references.pmid: 23660842
references.citation: Nat Struct Mol Biol. 2011 Oct;18(10):1139-46
references.pmid: 21909094
references.citation: PLoS One. 2013;8(6):e66676
references.pmid: 23826111
references.citation: J Biol Chem. 2010 Jun 4;285(23):17869-79
references.pmid: 20371610
references.citation: Nat Rev Genet. 2008 Feb;9(2):102-14
references.pmid: 18197166
references.citation: J Biol Chem. 2013 Jan 4;288(1):608-18
references.pmid: 23166327
references.citation: Oncogene. 2014 Feb 6;33(6):679-89
references.pmid: 23353819
references.citation: Cancer Gene Ther. 2012 Nov;19(11):773-8
references.pmid: 22996741
references.citation: Oncogene. 2013 Dec 12;32(50):5614-24
references.pmid: 23955085
references.citation: Mol Cell Biochem. 2013 Jul;379(1-2):201-11
references.pmid: 23568502
references.citation: Nat Rev Cancer. 2010 Jun;10(6):389-402
references.pmid: 20495573
references.citation: Nat Genet. 2007 Oct;39(10):1278-84
references.pmid: 17893677
references.citation: J Clin Endocrinol Metab. 2013 Aug;98(8):E1305-13
references.pmid: 23796566
references.citation: Gastroenterology. 2011 Nov;141(5):1749-61.e1
references.pmid: 21806946
references.citation: Pigment Cell Melanoma Res. 2011 Jun;24(3):538-50
references.pmid: 21466664
references.citation: Oncol Rep. 2012 Jun;27(6):1960-6
references.pmid: 22426647
references.citation: Nat Genet. 2005 May;37(5):495-500
references.pmid: 15806104
references.citation: Mol Cancer Ther. 2011 Aug;10(8):1337-45
references.pmid: 21666078
references.citation: Oncogene. 2008 Mar 27;27(14):2015-26
references.pmid: 17922033
references.citation: Invest New Drugs. 2012 Dec;30(6):2403-6
references.pmid: 22238073
references.citation: Cancer Epidemiol Biomarkers Prev. 2012 Aug;21(8):1236-43
references.pmid: 22736789
references.citation: J Orthop Res. 2014 May;32(5):695-701
references.pmid: 24501096
references.citation: J Biol Chem. 2011 Jan 21;286(3):1675-82
references.pmid: 20947507
references.citation: Mol Carcinog. 2014 Sep;53(9):711-21
references.pmid: 23661430
references.citation: Oncol Rep. 2013 Sep;30(3):1223-30
references.pmid: 23817566
references.citation: Biochim Biophys Acta. 2009 Jun;1792(6):497-505
references.pmid: 19268705
references.citation: J Surg Oncol. 2014 Mar;109(3):184-8
references.pmid: 24249252
references.citation: J Neurooncol. 2013 Nov;115(2):143-51
references.pmid: 23912551
references.citation: J Clin Bioinforma. 2013 Sep 28;3(1):17
references.pmid: 24073882
references.citation: Cancer Res. 2010 Apr 15;70(8):3119-27
references.pmid: 20354188
references.citation: Spine (Phila Pa 1976). 2010 Jun 1;35(13):1257-64
references.pmid: 20461036
references.citation: Hepatology. 2012 Nov;56(5):1631-40
references.pmid: 22610915
references.citation: Hepatology. 2013 Jun;57(6):2274-86
references.pmid: 23316018
references.citation: J Pathol. 1993 Dec;171(4):253-5
references.pmid: 8158454
references.citation: J Orthop Res. 2010 Jun;28(6):746-52
references.pmid: 20041488
references.citation: Cell Biol Int. 2008 Jul;32(7):733-8
references.pmid: 18400526
references.citation: Mol Cell Biol. 2008 Nov;28(22):6773-84
references.pmid: 18794355
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3111-6
references.pmid: 20133617
references.citation: Eur J Cancer. 2013 Feb;49(3):604-15
references.pmid: 23099007
references.citation: Mol Cancer Ther. 2009 Sep;8(9):2597-605
references.pmid: 19723879
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D140-4
references.pmid: 16381832
references.citation: Cancer Inform. 2007 Feb 04;3:11-7
references.pmid: 19455231
references.citation: J Biol Chem. 2012 Jan 20;287(4):2608-17
references.pmid: 22139839
references.citation: J Gastrointest Surg. 2013 Aug;17(8):1399-405
references.pmid: 23715647