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Differential expression of microRNAs in GH-secreting pituitary adenomas.doc

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Differential expression of microRNAs in GH-secreting pituitary adenomas

Maoetal.DiagnosticPathology2010,5:79 /content/5/1/79 RESEARCH OpenAccess DifferentialexpressionofmicroRNAsin GH-secretingpituitaryadenomas Zhi-GangMao1,Dong-ShengHe1,JingZhou2,BinYao3,Wei-WeiXiao2,Chun-HuaChen2, Yong-HongZhu2*,Hai-JunWang1* Abstract Background:Thepurposeofthisstudywasto(1)identifyspecificmiRNAsingrowthhormones(GH)-secreting pituitaryadenomas;(2)determinetherelationshipbetweentheexpressionofthesemiRNAsandtumorsize, somatostatinanalogstreatment,andresponsivenesstosomatostatinanalogs(SSA). Methods:FifteenGH-secretingadenomaspatientsweretreatedwithlanreotidefor4monthsbeforesurgery. Patientswith50%reductionofGHsecretionbylanreotidewereconsideredasSSAresponders,whilepatientswith lessthan50%ofGHreductionwereconsideredasSSAnonresponders.WeanalyzedthemiRNAsin21GH- secretingpituitaryadenomasand6normalpituitariesbymiRCURY?LNAarrayandsomedifferentiallyexpressed miRNAswerevalidatedbyquantitativereal-timePCR. Results:Fifty-twomiRNAsweredifferentiallyexpressedbetweenGH-secretingpituitaryadenomasandnormal pituitaries.Differentialexpressionof9miRNAswasobservedbetweenmicro-andmacro-adenomas.Thirteen miRNAsweredifferentiallyexpressedbetweentumorsamplesfromlanreotide-treatedpatientsandthosefrom lanreotide-untreatedpatients.SevenmiRNAsweredifferentiallyexpressedbetweenSSArespondersorGH nonresponders.SeveralidentifiedmiRNAsmaybeinvolvedincellproliferation,apoptosis,cancerdevelopmentand progression. Conclusions:OurresultsindicatethatalteredmiRNAsexpressionisinvolvedinGH-secretingpituitaryadenomas transformation,whichwillshedlightonthemechanismsforthetreatmentofacromegalybySSA.Identification andcharacterizationofthetargetsofalteredmiRNAsgenesmayelucidatemolecularmechanismsinvolvedinthe pathogenesisofpituitaryadenoma. Background signaling pathways, apoptosis and metabolism [5,6]. MicroRNAs(miRNAs)areaclass ofnon-coding RNAs Recently,ithasbeenshownthatseveralhumancancers, that post-transcriptionally regulate the expression of e.g. breast, colon, lung,brain, thyroid, an