title: Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice.
abstract: Mus spretus mice are highly resistant to several types of cancer compared to Mus musculus mice. To determine whether differences in microRNA (miRNA) expression account for some of the differences in observed skin cancer susceptibility between the strains, we performed miRNA expression profiling of skin RNA for over 300 miRNAs. Five miRNAs, miR-1, miR-124a-3, miR-133a, miR-134, miR-206, were differentially expressed by array and/or qPCR. miR-1 was previously shown to have tumor suppressing abilities in multiple tumor types. We found miR-1 expression to be lower in mouse cutaneous squamous cell carcinomas (cSCCs) compared to normal skin. Based on the literature and our expression data, we performed detailed studies on predicted miR-1 targets and evaluated the effect of miR-1 expression on two murine cSCC cell lines, A5 and B9. Following transfection of miR-1, we found decreased mRNA expression of three validated miR-1 targets, Met, Twf1 and Ets1 and one novel target Bag4. Decreased expression of Ets1 was confirmed by Western analysis and by 3' reporter luciferase assays containing wildtype and mutated Ets1 3'UTR. We evaluated the effect of miR-1 on multiple tumor phenotypes including apoptosis, proliferation, cell cycle and migration. In A5 cells, expression of miR-1 led to decreased proliferation compared to a control miR. miR-1 expression also led to increased apoptosis at later time points (72 and 96 h) and to a decrease in cells in S-phase. In summary, we identified five miRNAs with differential expression between cancer resistant and cancer susceptible mice and found that miR-1, a candidate tumor suppressor, has targets with defined roles in tumorigenesis.
authors: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Jessica L
authors: JL
authors: Fleming
authors: Biomedical Science Program, The Ohio State University, Columbus, OH, USA.
authors: Dustin L
authors: DL
authors: Gable
authors: Division of Hematology/Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
authors: Somayeh
authors: S
authors: Samadzadeh-Tarighat
authors: Biomedical Science Program, The Ohio State University, Columbus, OH, USA.
authors: Luke
authors: L
authors: Cheng
authors: The Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
authors: Lianbo
authors: L
authors: Yu
authors: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Jessica L
authors: JL
authors: Gillespie
authors: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
authors: Amanda Ewart
authors: AE
authors: Toland
keywords: Skin cancer; miR-1; microRNA
references: Carcinogenesis. 2012 Mar;33(3):572-80
references: 22232738
references: PLoS One. 2009;4(1):e4179
references: 19142229
references: Am J Pathol. 2009 Mar;174(3):736-45
references: 19179615
references: Oncol Rep. 2012 Aug;28(2):701-6
references: 22664953
references: Mol Cancer Res. 2012 Apr;10(4):504-15
references: 22343615
references: Nat Genet. 2006 Feb;38(2):228-33
references: 16380711
references: Oncogene. 2006 Mar 30;25(14):2022-9
references: 16301997
references: Cancer. 2000 Oct 15;89(8):1670-6
references: 11042559
references: Biochem Biophys Res Commun. 2008 Nov 21;376(3):548-52
references: 18801338
references: J Biol Chem. 2008 Nov 28;283(48):33394-405
references: 18818206
references: Cell Cycle. 2008 Aug 15;7(16):2485-92
references: 18719380
references: Genetics. 2007 Aug;176(4):2529-40
references: 17483433
references: Nature. 2009 Mar 26;458(7237):505-8
references: 19136944
references: Science. 2011 Feb 4;331(6017):550-3
references: 21292970
references: Trends Genet. 2009 May;25(5):234-41
references: 19361882
references: Cancer Res. 2010 Nov 1;70(21):8487-97
references: 20940404
references: Nat Rev Cancer. 2010 Feb;10(2):130-7
references: 20094047
references: Mol Cancer. 2003 Aug 20;2:29
references: 12971829
references: J Biol Chem. 2009 Oct 23;284(43):29596-604
references: 19710019
references: Cancer Cell. 2011 Nov 15;20(5):635-48
references: 22094257
references: Mol Cell. 2010 May 14;38(3):323-32
references: 20471939
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D149-53
references: 18158296
references: Nat Genet. 2009 Aug;41(8):882-4
references: 19561607
references: N Engl J Med. 2008 Mar 13;358(11):1160-74
references: 18337605
references: Wiley Interdiscip Rev Syst Biol Med. 2011 Nov-Dec;3(6):728-38
references: 21381218
references: Life Sci. 2012 Oct 5;91(11-12):440-447
references: 22963810
references: Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6585-92
references: 18006758
references: Oncogene. 2007 May 14;26(22):3291-310
references: 17496923
references: Int J Oncol. 2011 Nov;39(5):1099-107
references: 21701775
references: Cancer Lett. 2009 Oct 8;283(2):125-34
references: 19217204
references: J Invest Dermatol. 2010 Nov;130(11):2686-9
references: 20574436
references: Int J Oncol. 2012 Jun;40(6):1821-30
references: 22378464
references: Biochem Biophys Res Commun. 2000 May 10;271(2):409-13
references: 10799310
references: Stat Appl Genet Mol Biol. 2011 Sep 15;10(1):
references: 23089813
references: Nat Genet. 1996 Apr;12(4):455-7
references: 8630506
references: Oncogene. 2005 Aug 11;24(34):5384-8
references: 15940256
references: Int J Cancer. 2002 Mar 1;98(1):8-13
references: 11857377
references: J Cutan Pathol. 2004 Jan;31(1):8-13
references: 14675279
references: Exp Cell Res. 2013 Feb 1;319(3):77-88
references: 23142026
references: Hum Mol Genet. 2012 Feb 15;21(4):934-46
references: 22076443
references: J Pathol. 1999 Sep;189(1):40-5
references: 10451486
references: Biochem Biophys Res Commun. 2012 Jan 6;417(1):588-93
references: 22178073
references: Nat Genet. 1995 Aug;10(4):424-9
references: 7670492
references: Biochim Biophys Acta. 2008 Nov;1779(11):682-91
references: 18381085
references: Int J Oncol. 2009 Nov;35(5):989-96
references: 19787252
references: Oncotarget. 2012 Jan;3(1):9-21
references: 22308266
references: Oncotarget. 2011 Jan-Feb;2(1-2):29-42
references: 21378409
references: Int Heart J. 2009 May;50(3):377-87
references: 19506341
references: Nat Rev Genet. 2009 Oct;10(10):704-14
references: 19763153
references: Cancer Res. 2008 Jul 1;68(13):5049-58
references: 18593903
references: Mutat Res. 2011 Sep 1;714(1-2):126-33
references: 21616085
references: EMBO J. 2008 Feb 6;27(3):471-81
references: 18256698
references: Nucleic Acids Res. 2012 Apr;40(8):3689-703
references: 22210864
references: Nat Protoc. 2008;3(4):563-78
references: 18388938
references: Proc Natl Acad Sci U S A. 2007 May 8;104(19):8017-22
references: 17470785
references: Carcinogenesis. 2003 Jul;24(7):1159-65
references: 12807763
references: Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9740-4
references: 15210942
references: Cancer Lett. 2002 Dec 15;188(1-2):25-32
references: 12406544
references: Eur J Cancer. 2012 Apr;48(6):827-36
references: 21745735