MicroRNA Expression Is Down-Regulated and Reorganized in Prefrontal Cortex of Depressed Suicide Subjects 英文参考文献.docVIP

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MicroRNA Expression Is Down-Regulated and Reorganized in Prefrontal Cortex of Depressed Suicide Subjects 英文参考文献.doc

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MicroRNA Expression Is Down-Regulated and Reorganized in Prefrontal Cortex of Depressed Suicide Subjects 英文参考文献

MicroRNAExpressionIsDown-Regulatedand ReorganizedinPrefrontalCortexofDepressedSuicide Subjects NeilR.Smalheiser1,GiovanniLugli1,HooriyahS.Rizavi1,VetleI.Torvik2,GustavoTurecki3 ,Yogesh Dwivedi1* 1DepartmentofPsychiatry,PsychiatricInstitute,UniversityofIllinoisatChicago,Chicago,Illinois,UnitedStatesofAmerica,2GraduateSchoolofLibraryandInformation Science,UniversityofIllinoisatUrbana-Champaign,Champaign,Illinois,UnitedStatesofAmerica,3McGillGroupforSuicideStudies,McGillUniversity,Montreal,Quebec, Canada Abstract Background: Recent studies suggest that alterations in expression of genes, including those which regulate neural and structuralplasticity,maybecrucialinthepathogenesisofdepression.MicroRNAs(miRNAs)arenewlydiscoveredregulators ofgeneexpressionthathaverecentlybeenimplicatedinavarietyofhumandiseases,includingneuropsychiatricdiseases. Methodology/PrincipalFindings:ThepresentstudywasundertakentoexaminewhetherthemiRNAnetworkisalteredin the brain of depressed suicide subjects. Expression of miRNAs was measured in prefrontal cortex (Brodmann Area 9) of antidepressant-free depressedsuicide (n=18)andwell-matchednon-psychiatric control subjects(n=17)usingmultiplex RT-PCRplates.WefoundthatoverallmiRNAexpressionwassignificantlyandgloballydown-regulatedinprefrontalcortexof depressed suicide subjects. Using individual tests of statistical significance, 21 miRNAs were significantly decreased at p=0.05orbetter.Manyofthedown-regulatedmiRNAswereencodedatnearbychromosomalloci,sharedmotifswithinthe 59-seeds,andsharedputativemRNAtargets,severalofwhichhavebeenimplicatedindepression.Inaddition,asetof29 miRNAs, whose expression was not pairwise correlated in the normal controls, showed a high degree of co-regulation acrossindividualsinthedepressedsuicidegroup. Conclusions/Significance: The findings show widespread changes in miRNA expression that are likely to participate in pathogenesisofmajordepressionand/orsuicide.FurtherstudiesareneededtoidentifywhetherthemiRNAchangeslead toa