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MicroRNA Networks in Mouse Lung Organogenesis 英文参考文献.doc

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MicroRNA Networks in Mouse Lung Organogenesis 英文参考文献

MicroRNANetworksinMouseLungOrganogenesis JieDong1,GuoqianJiang2,YanW.Asmann2,SandraTomaszek1,JinJen3,ThomasKislinger4,5,DennisA. Wigle1* 1DivisionofGeneralThoracicSurgery,MayoClinicCancerCenter,MayoClinic,Rochester,Minnesota,UnitedStatesofAmerica,2DivisionofBiomedicalStatisticsand Informatics,DepartmentofHealthSciencesResearch,MayoClinic,Rochester,Minnesota,UnitedStatesofAmerica, 3PulmonaryMedicine,MayoClinicCancerCenter, Mayo Clinic, Rochester, Minnesota, United States of America, 4Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 5Ontario Cancer Institute,PrincessMargaretHospital,Toronto,Ontario,Canada Abstract Background:MicroRNAs(miRNAs)areknowntobeimportantregulatorsofbothorgandevelopmentandtumorigenesis. MiRNAnetworksandtheirregulationofmessengerRNA(mRNA)translationandproteinexpressioninspecificbiological processesarepoorlyunderstood. Methods:WeexploredthedynamicregulationofmiRNAsinmouselungorganogenesis.ComprehensivemiRNAandmRNA profiling was performed encompassing all recognized stages of lung development beginning at embryonic day 12 and continuing to adulthood. We analyzed the expression patterns of dynamically regulated miRNAs and mRNAs using a numberofstatisticalandcomputationalapproaches,andinanintegratedmannerwithproteinlevelsfromanexistingmass- spectrometryderivedproteindatabaseforlungdevelopment. Results: In total, 117 statistically significant miRNAs were dynamically regulated during mouse lung organogenesis and clusteredintodistincttemporalexpressionpatterns.11,220mRNAprobeswerealsoshowntobedynamicallyregulatedand clusteredintodistincttemporalexpressionpatterns,with3majorpatternsaccountingfor75%ofallprobes.3,067direct miRNA-mRNAcorrelationpairswereidentifiedinvolving37miRNAs.Twodefinedcorrelationpatternswereobservedupon integrationwithproteindata:1)increasedlevelsofspecificmiRNAsdirectlycorrelatingwithdownregulationofpredicted mRNA targets; and 2) increased levels of specific miRNAs directly correlating wit