LETTERTOTHEEDITORnpgCellResearch(2015):1-4.©2015IBCB,SIBS,CASAllrightsreserved1001-0602/15$32.00www.nature.com/crCircularRNAisenrichedandstableinexosomes:apromisingbiomarkerforcancerdiagnosisCellResearchadvanceonlinepublication3July2015;doi:10.1038/cr.2015.82DearEditor,CircularRNAs(circRNAs)arerecentlyidentifiedasanaturallyoccurringfamilyofwidespreadanddiverseendogenousnoncodingRNAsthatmayregulategeneexpressioninmammals[1-4].Theyareunusuallysta-bleRNAmoleculeswithcelltype-ordevelopmentalstage-specificexpressionpatterns[3,5].Exosomesaresmallmembranevesiclesofendocyticoriginsecretedbymostcelltypes.Theycontainaspecificcargoofprotein,mRNAandmicroRNAspecies,whichcanmodulaterecipientcellbehaviorsandmaybeusedasbiomarkersfordiagnosisofhumandiseases[6].Here,weshowforthefirsttimethepresenceofabundantcircRNAsinexo-somes.RNA-seqanalysesrevealedthatcircRNAswereenrichedinexosomescomparedtotheproducercells.Furthermore,thesortingofcircRNAstoexosomesmayberegulatedbychangesofassociatedmiRNAlevelsinproducercells,andmaytransferbiologicalactivitytorecipientcells.Additionally,morethan1000circRNAswereidentifiedinhumanserumexosomes.circRNAsoriginatedfromhumancancerxenograftscouldenterthecirculationandbereadilymeasuredintheserum.Intrigu-ingly,serumexosomalcircRNAswereabletodistinguishpatientswithcoloncancerfromhealthycontrols.OurresultslaythefoundationfordevelopmentofcircRNAsasanewclassofexosome-basedcancerbiomarkersandsuggestthepotentialbiologicalfunctionofexosomalcir-cRNAs.FirstwecharacterizedcircRNAtranscriptsbyusingRNA-seqanalysesofribosomalRNA-depletedtotalRNAfromMHCC-LM3livercancercellsandcell-de-rivedexosomes(Supplementaryinformation,FigureS1).Thepreparedexosomeswereexaminedbytransmissionelectronmicroscopy(Supplementaryinformation,Fig-ureS2).Acomputationalpipeline[3]basedonanchoralignmentofunmappedreadswasusedtoidentifycir-cRNAs.Countsofreadsmappingacrossanidentifiedbacksplicearenormalizedbyreadlengthandnumberofreadsmapping(splicedreadsperbillionmapping(SRPBM)),whichallowsquantit...
