Genetic variants of miRNA sequences and non–small cell lung cancer survival

RecentevidenceindicatesthatsmallnoncodingRNAmoleculesknownasmicroRNAs�(miRNAs)�canfunc- tionastumorsuppressorsandoncogenes.�Mutation,�misexpression,�andalteredmaturemiRNAprocessing� areimplicatedincarcinogenesisandtumorprogression.�BecauseSNPsinpre-miRNAscouldaltermiRNA� processing,�expression,�and/orbindingtotargetmRNA,�weconductedasystematicsurveyofcommonpre- miRNASNPsandtheirsurroundingregionsandevaluatedindetailtheassociationof�4�oftheseSNPswith� thesurvivalofindividualswithnon-smallcelllungcancer�(NSCLC).�Whenweassumedthatdiseasesuscep- tibilitywasinheritedasarecessivephenotype,�wefoundthatthers11614913�SNPinhsa-mir-196a2�wasassoci- atedwithsurvivalinindividualswithNSCLC.�Specifically,�survivalwassignificantlydecreasedinindividuals� whowerehomozygousCCatSNPrs11614913.�Inthegenotype-phenotypecorrelationanalysisof�23�human� lungcancertissuesamples,�rs11614913�CCwasassociatedwithastatisticallysignificantincreaseinmature� hsa-mir-196aexpressionbutnotwithchangesinlevelsoftheprecursor,�suggestingenhancedprocessingof� thepre-miRNAtoitsmatureform.�Furthermore,�bindingassaysrevealedthatthers11614913�SNPcanaffect� bindingofmaturehsa-mir-196a2-3ptoitstargetmRNA.�Therefore,�thers11614913�SNPinhsa-mir-196a2�may� beaprognosticbiomarkerforNSCLC.�FurthercharacterizationofmiRNASNPsmayopennewavenuesfor� thestudyofcancerandtherapeuticinterventions.