环状RNA与人类疾病

ISSN1007-7626CN11-3870/Qhttp//cjbmb．bjmu．edu．cnChineseJournalofBiochemistryandMolecularBiology20158318771～7782015-01-142015-03-21No．81171660No．LY14C060003No．2014C33222No．201498No．201388No．2015A610236No．201501*[e-mail][e-mail]142015AcceptedMarch212015SupportedbyNationalNaturalScienceFoundationofChinaNo．81171660ZhejiangProvincialNaturalScienceFoundationofChinaNo．LY14C060003AppliedＲesearchProjectonNonprofitTechnologyofZhejiangProvinceNo．2014C33222ZhejiangProvinceＲegionalMedicalCenterProjectNo．201498NingboClinicalSpecialtyProjectNo．201388NingboNaturalScienceFoundationNo．2015A610236andZhejiangKeyLaboratoryofPathophysiologyNo．201501*[e-mail][e-mail]··DOI10.13865/j．cnki．cjbmb．2015.08.01ＲNA122*1*13152112315020ＲNAcircularＲNAscircＲNAsＲNA．circＲNAＲNAＲNACDＲ1asmiＲ-7、、．cANＲIL．circＲNA、．ＲNAＲNAＲNAQ522CircＲNAsandHumanDiseasesFULi-Yun12HUYao-Ｒen2*GUOJun-Ming1*1DepartmentofBiochemistryandMolecularBiologyNingboUniversitySchoolofMedicineZhejiangKeyLaboratoryofPathophysiologyNingbo315211China2DepartmentofHepatologyNingboNo．2HospitalNingbo315020ChinaAbstractCircularＲNAscircＲNAsrepresentaclassofwidespreadnon-codingＲNAsthatregulategeneexpression．Theyshareastablestructureandtissue-specificexpressionandotherfeatures．HarboringmicroＲNAsmiＲNAscompetitionsitessomecircＲNAsmayactascompetingendogenousＲNAs．ForexampleCDＲ1asspongingmiＲ-7isrelatedwithpathogenesisoflungcancerbreastcancergliomaandamyotrophiclateralsclerosisetc．cANＲILaffectsatherosclerosisthroughPolycombproteinfamilymembers．WithanoverwhelmingnumberofidentifiedcircＲNAsinhumansin-depthstudyofthestructureandfunctionofcircＲNAsmaynotonlypushustodisclosemechanismsofsomediseasesbutalsoprovideanewdirectionforthepreventiondiagnosisandtreatmentofdisorders．KeywordscircularＲNAscompetingendogenousＲNAmicroＲNAspongegeneexpressionregulationＲNAnon-codingＲNAncＲNA1．ＲNAcircularＲNAcircＲNA31ncＲNA．circＲNAＲNAcompetingendogenousＲNAceＲNA．1circＲNAcircＲNA2070ＲNA23．1990SaccharomycescircＲNA．5'3'20SＲNAhepatitisDvirusHDV4．circＲNAdeleteincolorectalcarcinomageneDCC5、Ets-1E-Twenty-Six-1Ets-16、sexdeterminingregionYSＲY7、P4502C248INK4ＲNAcircularantisensenon-codingＲNAintheINK4locuscANＲIL9“”．circＲNA10．Salzman11circＲNA．Jeck1225000circＲNA．Memczak13ＲNA1950circＲNA1903circＲNA724circＲNA．Guo14397112circＲNA．circＲNA3ＲNAexoniccircＲNA11-1315ＲNAcircularintronicＲNAciＲNA16ＲNAretained-introncircＲNA17．circＲNA110112ＲNaseＲ11123101141556ncＲNA7ceＲNA815．2circＲNAcircＲNAFig．1．Fig．1BiogenesisandfunctionsofcircＲNAsaExoniccircＲNAsareformedthrough‘headtotail’splicejunctionbExoniccircＲNAsaretransportedfromnucleustocytoplasmandcanfunctionasamiＲNAspongecCircularintronicＲNAsareformedthroughescapingdebranchingenzymesandthenmodulatetranscriptiondCircＲNAscanbeusedastemplatesforproteinsynthesisregulatorsofproteinandsoon．IＲESinternalribosomeentrysitemiＲNAmicroＲNA2778ＲNA2.1miＲNASalmena1820117ceＲNA．ceＲNAmiＲNAmiＲNAresponseelementMＲEceＲNAMＲEmiＲNAmiＲNAmiＲNA．circＲNAmiＲNAmiＲNAmiＲNA．circＲNAA5'、19miＲNA1320．circＲNA1antisensetothecerebellardegeneration-relatedprotein1transcriptCDＲ1asSＲY．CDＲ1asHansen212011．132074ＲNA-7microＲNA-7miＲ-7MＲE“”．miＲ-7miＲ-722．CDＲ1asmiＲ-7ＲNAcircularＲNAspongeformiＲ-7CiＲS-722．circＲNACDＲ1asmiＲNA14．CDＲ1asmiＲ-7miＲ-7CDＲ1asmiＲ-718．Memczak133-miＲ-7CDＲ1as．miＲ-7CDＲ1asmiＲ-7．Hansen21miＲ-671CDＲ1asCDＲ1asmiＲ-671CDＲ1asmiＲ-7．SＲYcircＲNA23-25．Hansen21SＲYcircＲNACDＲ1asmiＲ-13816MＲEmiＲ-138．2.2Zhang16circＲNAciＲNA．52ci-ankyrinrepeatdomain52ci-ankrd52ＲNAIIII．7silentinformationregulator7ci-sirt716．INK4/AＲFＲNA-ANＲILPcGINK4/AＲFcANＲIL9．2.3ＲNAcircＲNA．CDＲ1asSrymiＲNAargonauteAGO1320ci-ankrd52ＲNAII16．Bohjanen26transactivatingregulatoryproteinTatcircＲNA11humanimmunodeficiencyvirustype1HIV-1．2.4circＲNA27．5'3'AmＲNAcircＲNAinternalribosomeentrysiteIＲES14．hepatitisDvirusHDVcircＲNAHDVhepatitisDvirusantigenHDAg28．U2OScircＲNA14．circＲNA14．Talhouarne29ciＲNA1000ntＲNaseＲ．ciＲNAＲNA．3circＲNAcircＲNA377319222830-56Table1．Table1DiseasesandtheirrelatedcircＲNAsDiseasesＲelatedcircＲNAsＲeferencesTumorLungcancerCDＲ1as2232414445GastriccancerCDＲ1as2237ＲenalcancerCDＲ1as2246CervicalcancerCDＲ1as2245BreastcancerCDＲ1as2231323539GliomaCDＲ1as22303240SchwannomaCDＲ1as2233HepatocellularcarcinomaCDＲ1as2234ColorectalcancerCDＲ1ascirc0817circ3204circ6229circ7374224243AtherosclerosisCANＲIL9Parkinson’sdiseaseCDＲ1as48AmyotrophiclateralsclerosisCiＲNA49DiabetesCDＲ1as51PriondiseaseCDＲ1as54HepatitisHDVＲNA2855563.1circＲNA．．CDＲ1asmiＲ-7CDＲ1as/miＲ-722Fig．2．miＲ-7epidermalgrowthfactorreceptorEGFＲ30、1insulinreceptorsubstrate-1IＲS-130、IＲS-230、p21-1p21-activatedkinase-1Pak131、Ｒaf132、CDC421activatedCDC42kinase1Ack133-3δphosphatidylinositol3-kinasecatalyticsubunitδPIK3CD34．miＲ-7EGFＲBproteinkinaseBPKBIＲS-1IＲS-230．Pak1miＲ-7Pak1HOXD10．Pak1miＲ-7HOXD10．miＲ-7、．miＲ-7/Pak1Fig．2CDＲ1as/miＲ-7andtumorThebalanceofCDＲ1as/miＲ-7impactsalotofcytokinesoncogenessignalpathwaysandcancerstemcellCSCduringtumorigenesisandmetastasis．EGFＲepidermalgrowthfactorreceptorIＲS-1insulinreceptorsubstrate-1IＲS-2insulinreceptorsubstrate-2Pak1p21-activatedkinase