简介:N^6-methyladenosine(m^6A)isanessentialRNAmodificationthatregulateskeycellularprocesses,includingstemcellrenewal,cellulardifferentiation,andresponsetoDNAdamage.Unsurprisingly,aberrantm6Amethylationhasbeenimplicatedinthedevelopmentandmaintenanceofdiversehumancancers.Alteredm6AlevelsaffectRNAprocessing,mRNAdegradation,andtranslationofmRNAsintoproteins,therebydisruptinggeneexpressionregulationandpromotingtumorigenesis.Recentstudieshavereportedthattheabnormalexpressionofm6Aregulatoryenzymesaffectsm6Aabundanceandconsequentlydysregulatestheexpressionoftumorsuppressorgenesandoncogenes,includingMYC,SOCS2,ADAM19,andPTEN.Inthisreview,wediscussthespecificrolesofm6A“writers",“erasers”,and“readers”innormalphysiologyandhowtheiralteredexpressionpromotestumorigenesis.Wealsodescribethepotentialofexploitingtheaberrantexpressionoftheseenzymesforcancerdiagnosis,prognosis,andthedevelopmentofnoveltherapies.
简介:AIM:Toinvestigatewhethergenemethylationintheperitonealfluid(PF)predictsperitonealrecurrenceingastriccancerpatients.METHODS:ThegenemethylationofCHFR(checkpointwithforkheadandringfingerdomains),p16,RUNX3(runt-relatedtranscriptionfactor3),E-cadherin,hMLH1(mutLhomolog1),ABCG2(ATP-bindingcassette,sub-familyG,member2)andBNIP3(BCL2/adenovirusE1B19kDainteractingprotein3)wereanalyzedin80specimensofPFbyquantitativemethylation-specificpolymerasechainr...
简介:TheroleofthetranscriptionfactorNF-κBinshapingthecancermicroenvironmentisbecomingincreasinglyclear.InflammationalterstheactivityofenzymesthatmodulateNF-κBfunction,andcausesextensivechangesingenomicchromatinthatultimatelydrasticallyaltercell-specificgeneexpression.NF-κBregulatestheexpressionofcytokinesandadhesionfactorsthatcontrolinteractionsamongadjacentcells.Assuch,NF-κBfinetunestissuecellularcomposition,aswellastissues'interactionswiththeimmunesystem.Therefore,NF-κBchangesthecellresponsetohormonesandtocontactwithneighboringcells.ActivatingNF-κBconferstranscriptionalandphenotypicplasticitytoacellandtherebyenablesprofoundlocalchangesintissuefunctionandcomposition.ResearchsuggeststhattheregulationofNF-κBtargetgenesisspecificallyalteredincancer.SuchalterationsoccurnotonlyduetomutationsofNF-κBregulatoryproteins,butalsobecauseofchangesintheactivityofspecificproteostaticmodulesandmetabolicpathways.ThisarticledescribesthemolecularmodeofNF-κBregulationwithafewcharacteristicexamplesoftargetgenes.
简介:ObjectiveToinvestigatethehypermethylationstatusofglutathionetransferaseP1(GSTP1)andE-cadherin(ECAD),TSGs(tumorsuppressorgenes)inourbreastcancersamplesandexploretheircorrelationwithclinicopathologicalfeaturesofcorrespondingcancerpatients.MethodsOnehundredandthirty-sixIDC(invasiveductalcarcinoma)patientswererecruitedforanalysisand16fibroadenomapatientsactedascontrol.DNAextractionandmethylation-specificPCR(MSP)weresubsequentlyperformedprecededbypathologicalexamination.ResultsThepercentageofhypermethylatedGSTP1incarcinomaandfibroadenomagroupswas34.92%and15.79%respectivelyandthepercentageofhypermethylatedECADincarcinomasandfibroadenomaswas18.00%and0.00%respectively.Carcinomahadthehighestpercentageofc-erbB2overexpressionbeing54.55%amongtheclinicopathologicalparameters.ConclusionHypermethylationpatternsarefrequentinIDCandseemtorelatetoc-erbB2overexpression,andsuchepigeneticchangeshouldnotbeneglectedinfibroadenoma.Tumormethylationstatusincancerpatientscanbedeterminedatearlystageanditmaybeareferenceforbettertreatmentplanning.
简介:Thematrixmetalloproteinases(MMPs)areafamilyofzine-dependentendopeptidasesthatplayakeyroleinbothnormalandpathologicalprocessesinvolvingtissueremodelingevents.Theexpressionoftheseproteolyticenzymesishighlyregulatedbyabalancebetweenextracellularmatrix(ECM)depositionanditsdegradation,andiscontrolledbygrowthfactors,cytokines,hormones,aswellasinteractionswiththeECMmacromolecules.Furthermore,theactivityoftheMMPsisregulatedbytheirnaturalendogenousinhibitors,whicharemembersofthetissueinhibitorofmetalloproteinases(TIMP)family.Inthenormalmammarygland,MMPsareexpressedduringductaldevelopment,lobulo-alveolardevelopmentinpregnancyandinvolutionafterlactation.Underpathologicalconditions,suchastumorigenesis,thedysregulatedexpressionofMMPsplayaroleintumorinitiation,progressionandmalignantconversionaswellasfacilitatinginvasionandmetastasisofmalignantcellsthroughdegradationoftheECMandbasementmembranes.
简介:AIM:ToscreenmicroRNAs(miRNAs)andsetuptargetmiRNAsinpterygium.METHODS:PrimaryfibroblastswereisolatedfrompterygiumandTenon’scapsuleandcultured.ImmunocytochemicalanalysisandWesternblottingwereperformedtoconfirmthecultureoffibroblasts.Inall,1733miRNAswerescreenedinthefirststepbyusingGeneChip?miRNA3.0Array.SpecificmiRNAsinvolvedinthepathogenesisofpterygiumweresubsequentlydeterminedusingthefollowingcriteria:1)highreproducibilityinarepetitivetest;2)baselogvalueof>7.0forbothcontrolandpterygialfibroblasts;and3)logratioof>1.0betweenpterygialfibroblastsandcontrolfibroblasts.RESULTS:Primaryscreeningshowedthat887/1733miRNAswereup-regulatedand846/1733miRNAsweredown-regulatedinpterygialfibroblastscomparedwiththoseincontrolfibroblasts.Ofthe1733miRNAsscreened,4miRNAs,namely,miRNA-143a-3p,miRNA-181a-2-3p,miRNA-377-5pandmiRNA-411a-5p,mettheabove-mentionedcriteria.Primaryscreeningshowedthatthese4miRNAswereup-regulatedinpterygialfibroblastscomparedwithcontrolfibroblastsandthatmiRNA-143a-3phadthehighestmeanratiocomparedwiththemiRNAsincontrolfibroblasts.CONCLUSION:miRNA-143a-3p,miRNA-181a-2-3p,miRNA-377-5pandmiRNA-411a-5pareup-regulatedinpterygialfibroblastscomparedwithcontrolfibroblasts,suggestingtheirinvolvementinthepathogenesisofpterygium.
简介:Objective:ToconstructtherecombinantplasmidcontainingGlycerophosphodiesterphosphodiesterase(Gpd)genefromTreponemapallidumandtransfectitintoHelacellstoexpresstheencodedoutermembraneprotein.Methods:TheGpdgenewasamplifiedfromthegenomicDNAofT.pallidumbypolymerasechainreaction(PCR)andinsertedintocloningvectorpUCm-T.TheinsertedGpdgenewassubclonedintotheappropriatesiteofpcDNA3.1(+)vector.Afteridentificationbysequencingandrestrictiveenzymesdigestion,therecombinantplasmidwastransfectedintoHelacellsusingliposomes.TheexpressedproteinwasidentifiedbyimmunocytochemistryandWesternblot.Results:ThetargetGpdgenesegmentwasapproximately1059bp.TheDNAsequenceoftheGpdgenecontainedinthepcDNA3.1(+)vectorwasconsistentwiththepublishednucleotidesequence.ThehomologyofthenucleotideandputativeaminoacidsequencesoftheGpdgenebetweenT.pallidumsubsp.pallidumNicholsandvariouspathogenictreponemalstrainsrangedfrom98%to100%.ImmunocytochemistryandWesternblotanalysisshowedthattheconstructedGpd-pcDNA3.1(+)vectorexpressedafusionproteinwithacalculatedmolecularmassof41KDainHelacellsandthattheexpressedproteinreactedwiththeserafromsyphilispatients.Conclusion:ThesuccessfulconstructionandexpressionoftheeukaryoticexpressionplasmidoftheGpdgenefromT.pallidumprovideapromisingtooltofurtherstudythebiologicalactivityofT.pallidumanddevelopaDNAvaccineforsyphilis.
简介:Duringtheevolvementofarchitecture,theresearchonarchitecturalformandstructureaswellasdifferentwaystoexpressandrealizearchitecturalthoughtsisconstantlythefocusofmanyarchitects,Thispaperillustratesthemutualinfluenceofthewaysofexpressionanddesignofarchitecturetopeople'sunderstandingofthemeaningofarchitecturethroughoutthehistoryoftheireffortsandexploration.thepaperalsodiscussestheextensiveusageofvirtual-realithapproachthroughcomputertechnology,Itpointsoutthatthetraditionalarchitecturalstandpointwillundergobreakthroughbytheemergenceofnewexpressionanddesignmethod.Inthisway,people'sunderstandingofarchitecturewillbemoreprofoundandlasting.
简介:Objective:Toclone,sequenceandexpresstheprimateβ-chemokineRANTESgenes,hRANTESfromH.sapiensandmRANTESfromM.Mulatta,inordertoexplorethepossibilityofAIDSgenetherapy.Methods:hRANTESandmRANTESwereamplifiedbyreversetranscription-polymerasechainreaction(RT-PCR)fromRNAsextractedfromphytoagglutinin(PHA)-activatedperipheralbloodlymphocytes,hRANTESwascloned,sequencedandexpressedinvitro,andmRANTESwasdirectlysequencedforhomologycomparison.Results:Anexpected276bpfragmentwasobtainedinbothamplifications,andsequencedatademonstratedarelativelyhighhomologyamongdifferentcopiesofhRANTES(97%),andhRANTESwasupto95.6%homologoustomRANTES.WhencomparedwithRANTESfromothermammals,hRANTESgaverisetoahomologyrangingfrom77%to86%.TheclonedhRANTESwasexpressedinvitroandapositivesignalofRANTESwasdetectedbydotblotting.Conclusion:Thefull-lengthofhRANTESsequencewassubmittedtoGenBankandhadbeenreleased.OurmRANTESsequenceisfirstreportedandnotyetappearedinGenBank.ThesuccessfulcloningandexpressionofhRANTESwillprovideabasisforAIDSgenetherapyinthefuture.