Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer

Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer

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1、BreastCancerResTreat(2011)127:69–80DOI10.1007/s10549-010-0972-2PRECLINICALSTUDYLet-7familymiRNAsregulateestrogenreceptoralphasignalinginestrogenreceptorpositivebreastcancerYingchunZhao•CaishuDeng•JiaruiWang•JingXiao•ZoranGatalica•RobertR.Recker•GaryGuishanXiaoReceived:10March2010/Accepted:26M

2、ay2010/Publishedonline:10June2010ÓSpringerScience+BusinessMedia,LLC.2010AbstractInordertounderstandhowmicroRNAs(miR-processinMCF7cells.Inconclusion,ourfindingsindicateNAs)regulatebreastcancertumorigenesis,amiRNAanewregulatorymechanismoflet-7miRNAsinER-aexpressionmicroarrayscreeningwasperformed

3、usingmediatedcellularmalignantgrowthofbreastcancer.RNAfromformalin-fixedparaffin-embedded(FFPE)breasttissues,whichincludedbenign(n=13),ductalKeywordsLet-7familymicroRNAsBreastcancercarcinomainsitu(DCIS)(n=16),andinvasiveductalFFPEEstrogenreceptor-asignalingcarcinoma(IDC)(n=15).Twenty-fivediff

4、erentiallyexpressedmiRNAs(P.01)wereidentified,ofwhichAbbreviationslet-7familymiRNAsweredown-regulatedinhumanbreastANOVAAnalysisofvariancecancertissuesatstagesofDCISandIDCcomparedtoBT-ICBreasttumor-initiatingcellsbenignstage.WefurtherfoundthattherewasaninverseDCISDuctalcarcinomainsitucorrelat

5、ionbetweenER-aexpressionandseveralmembersDMSODimethylsulfoxideoflet-7familyintheFFPEtissues.Next,weperformedE217-b-Estradiolbioinformaticsanalysisandfoundthatlet-7miRNA0EREstrogenreceptorsequencesmatchsequenceinthe3-UTRofestrogenER-aERalphareceptoralpha(ER-a),suggestingER-amaybeatargetofEREEs

6、trogenresponseelementlet-7,whichwasfurtherconfirmedbyanumberofexper-FBSFetalbovineserumimentalassays,includingluciferaseassay,proteinexpres-FFPEFormalin-fixedparaffin-embeddedsion,andmRNAexpression.Overexpressionoflet-7IDCInvasiveductalcarcinomamiRNAsinER-positivebreastcancerMCF7celllinemiRNAmic

7、roRNAnegativelyaffectedER-aactivity.Asexpected,dampeningMTT3-[4,5-Dimethylthiazol-2-yl]-2,5-oftheER-asignalingbylet-7miRNAsinhibitedcelldiphenyltetrazoliumbromideproliferation,andsubsequentlytriggeredthecellapoptotic003-UTR3-Untranslatedregio

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