REVIEWOpenAccessTranslationandfunctionalrolesofcircularRNAsinhumancancerMingLei1,2,GuantaoZheng1,2,QianqianNing1,2,JunnianZheng1,2*andDongDong1,2*AbstractCircularRNAs(circRNAs)areanewclassofnon-codingRNAsformedbycovalentlyclosedloopsthroughbacksplicing.Recentmethodologieshaveenabledin-depthcharacterizationofcircRNAsforidentificationandpotentialfunctions.CircRNAsplayimportantrolesinvariousbiologicalfunctionsasmicroRNAsponges,transcriptionalregulatorsandcombiningwithRNAbindingproteins.RecentstudiesindicatedthatsomecytoplasmiccircRNAscanbeeffectivelytranslatedintodetectablepeptides,whichenlightenedusontheimportanceofcircRNAsincellularphysiologyfunction.InternalRibosomeEntrysite(IRES)-andN6-methyladenosines(m6A)-mediatedcap-independenttranslationinitiationhavebeensuggestedtobepotentialmechanismforcircRNAtranslation.Todate,severaltranslatedcircRNAshavebeenuncoveredtoplaypivotalrolesinhumancancers.Inthisreview,weintroducedthepropertiesandfunctionsofcircRNAs,andcharacterizedthepossiblemechanismoftranslationinitiationandcomplexityofthetranslationabilityofcircRNAs.WesummarizedtheemergingfunctionsofcircRNA-encodedproteinsinhumancancer.TheworksoncircRNAtranslationwillopenahiddenhumanproteome,andenhanceustounderstandtheimportanceofcircRNAsinhumancancer,whichhasbeenpoorlyexploredsofar.Keywords:CircularRNA,Translation,Function,Cancer,BiomarkerBackgroundCircularRNAs(circRNAs)areanewtypeofendogenousRNAsproducedbynon-canonicalback-splicingevents[1,2].IncircRNA,thedownstreamsplice-donorsitecanbecovalentlylinkedtoanupstreamsplice-acceptorsite.ThefirstcircRNAmoleculewasdiscoveredinanRNAvirusin1976[3,4],andcircRNAswereobservedineukaryoticcelllinesbyelectronmicroscopyin1991[5].Thereafter,circRNAshavelongbeenconsideredasaber-rantsplicingevents[6].GenomicandtranscriptomicdatageneratedbynextgenerationsequencingprojectsandbioinformaticsalgorithmshaveidentifiedsignificantamountofcircRNAsineukaryotes[7–14],clearlydem-onstratingthattheyarenotmerelytheaccidentalbypro-ductsor‘splicingnoise’...
