Dysregulation of MicroRNA-34a Expression in Head and Neck Squamous Cell Carcinoma Promotes Tumor Growth and Tumor Angiogenesis 英文参考文献.docVIP
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Dysregulation of MicroRNA-34a Expression in Head and Neck Squamous Cell Carcinoma Promotes Tumor Growth and Tumor Angiogenesis 英文参考文献
DysregulationofMicroRNA-34aExpressioninHeadand
NeckSquamousCellCarcinomaPromotesTumorGrowth
andTumorAngiogenesis
BhavnaKumar1,2,ArtiYadav2,JamesLang1,2,TheodorosN.Teknos1,2,PawanKumar1,2
*
1Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Columbus, Ohio, United States of America, 2The Ohio State University
ComprehensiveCancerCenter,TheOhioStateUniversity,Columbus,Ohio,UnitedStatesofAmerica
Abstract
Background:MicroRNAs(miRs)aresmallnon-codingRNAsthatplayanimportantroleincancerdevelopmentwherethey
canactasoncogenesorastumor-suppressors.miR-34aisatumor-suppressorthatisfrequentlydownregulatedinanumber
oftumortypes.However,littleisknownabouttheroleofmiR-34ainheadandnecksquamouscellcarcinoma(HNSCC).
MethodsandResults:miR-34aexpressionintumorsamples,HNSCCcelllinesandendothelialcellswasexaminedbyreal
time PCR. Lipofectamine-2000 was used to transfect miR-34a in HNSCC cell lines and human endothelial cells. Cell-
proliferation, migration and clonogenic survival was examined by MTT, Xcelligence system, scratch assay and colony
formationassay.miR-34aeffectontumorgrowthandtumorangiogenesiswasexaminedbyinvivoSCIDmousexenograft
model. Our results demonstrate that miR-34a is significantly downregulated in HNSCC tumors and cell lines. Ectopic
expressionofmiR-34ainHNSCCcelllinessignificantlyinhibitedtumorcellproliferation,colonyformationandmigration.
miR-34a overexpression also markedly downregulated E2F3 and survivin levels. Rescue experiments using microRNA
resistant E2F3 isoforms suggest that miR-34a-mediated inhibition of cell proliferation and colony formation is
predominantly mediated by E2F3a isoform. In addition, tumor samples from HNSCC patients showed an inverse
relationshipbetweenmiR-34aandsurvivinaswellasmiR-34aandE2F3levels.OverexpressionofE2F3acompletelyrescued
survivinexpressioninmiR-34aexpressingcells,therebysuggestingthatmiR-34amayberegulatingsurvivinexpressionvia
E2F3a.EctopicexpressionofmiR-34aalsosignificantlyinhibitedtumorgrowt
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