REVIEWOpenAccessThenovelrolesofcircRNAsinhumancancerQingfengShang1,2†,ZhiYang1,2,3†,RenbingJia1,2*andShengfangGe1,2*AbstractCovalentlyclosedsingle-strandedcircularRNAs(circRNAs)consistofintronsorexonsandarewidelypresentineukaryoticcells.CircRNAsgenerallyhavelowexpressionlevelsandrelativelystablestructurescomparedwithmessengerRNAs(mRNAs),mostofwhicharelocatedinthecytoplasmandoftenactincelltypeandtissue-specificmanners,indicatingthattheymayserveasnovelbiomarkers.Inrecentyears,circRNAshavegraduallybecomeahotspotinthefieldofRNAandcancerresearch,butthefunctionsofmostcircRNAshavenotyetbeendiscovered.KnowncircRNAscanaffectthebiogenesisofcancersindiverseways,suchasfunctioningasamicroRNA(miRNA)sponges,combiningwithRNAbindingproteins(RBPs),workingasatranscriptionfactorandtranslationofproteins.Inthisreview,wesummarizethecharacteristicsandtypesofcircRNAs,introducethebiogenesisofcircRNAs,discusstheemergingfunctionsanddatabasesoncircRNAsandpresentthecurrentchallengesofcircRNAsstudies.Keywords:CircRNAs,Cancer,Sponge,Translation,DatabaseBackgroundInthepastfewdecades,thefieldofRNA,especiallythenon-codingRNA(ncRNA)field,hasbenefittedfromtherapiddevelopmentandapplicationofhigh-throughputRNAsequencing(RNA-seq)technology[1].Themajor-ityofRNAspeciesineukaryoticcellsiscomprisedofncRNAratherthanmessengerRNA(mRNA),andstudieshaveshownthatthesencRNAsplayavitalroleinphysiologicalanddevelopmentalprocesses.Inprevi-ousstudies,scientistsmainlyfocusedonlinearncRNAs,suchaslongnon-codingRNAs(lncRNAs)andmicro-RNAs(miRNAs),indicatingthattheselinearncRNAshavemultiplefunctionsinphysiologicalandpathologicalprocesses.AsakindofuniquecircularncRNA,circularRNAs(circRNAs)havebeenpreviouslyconsideredaccidentalby-productsor‘splicingnoise’withlowabundanceandlittlefunctionalpotential,resultingfromerrorsduringpost-transcriptionalprocessing[2].ThefirstcircRNAswerefoundintheSendaivirusandplant-infectedviroidsin1976byKolakofskyandSanger,respectively[3,4].Subsequently,onlyafewcircRNAswithorwithoutbiologicalfunct...
