長鏈非編碼RNA RP11-325L7.1在胃腺癌中的表達及其功能的初步研究

長鏈非編碼RNARP11-325L7.1在胃腺癌中的表達及其功能的初步研究摘要：長鏈非編碼RNA在腫瘤中的表達和功能受到越來越多的關(guān)注。本研究主要探討長鏈非編碼RNARP11-325L7.1在胃腺癌中的表達及其功能。通過實時熒光定量PCR檢測，發(fā)現(xiàn)RP11-325L7.1在胃腺癌組織中顯著上調(diào)。同時，通過RNA干擾技術(shù)，發(fā)現(xiàn)RP11-325L7.1敲低可顯著抑制胃癌細胞的增殖能力。進一步研究發(fā)現(xiàn)，RP11-325L7.1敲低后可明顯抑制胃癌細胞的遷移和侵襲。機制研究表明，RP11-325L7.1敲低可降低胃癌細胞內(nèi)MatrixMetalloproteinase2(MMP2)的表達，從而抑制其遷移和侵襲能力。綜合以上結(jié)果，RP11-325L7.1在胃腺癌中起著促進胃癌進展的作用，可作為胃癌的潛在治療靶標(biāo)。

關(guān)鍵詞：長鏈非編碼RNA，RP11-325L7.1，胃腺癌，RNA干擾，MatrixMetalloproteinase2

Abstract:Longnon-codingRNAs(lncRNAs)haveattractedincreasingattentionincancerresearchbecauseoftheirdiverseexpressionandfunctionalroles.Inthisstudy,weinvestigatetheexpressionandfunctionalroleoflncRNARP11-325L7.1ingastricadenocarcinoma.Real-timePCRanalysisshowedthatRP11-325L7.1wassignificantlyup-regulatedingastriccancertissuescomparedtoadjacentnormaltissues.Furthermore,knockdownofRP11-325L7.1significantlyinhibitedtheproliferation,migrationandinvasionofgastriccancercells.MechanisticstudiesrevealedthatknockdownofRP11-325L7.1reducedtheexpressionofMatrixMetalloproteinase2(MMP2)ingastriccancercells,whichwasassociatedwithadecreaseincellmigrationandinvasion.Collectively,ourresultssuggestthatRP11-325L7.1functionsasanoncogeniclncRNAingastricadenocarcinoma,andmayserveasapotentialtherapeutictargetforgastriccancer.

Keywords:longnon-codingRNA,RP11-325L7.1,gastricadenocarcinoma,RNAinterference,MatrixMetalloproteinaseGastricadenocarcinomaisoneofthemostcommonmalignanciesworldwide,withhighmorbidityandmortalityrates.Theidentificationofnoveltherapeutictargetsandbiomarkersfordiagnosisandprognosticationofgastriccancerisofgreatimportance.Longnon-codingRNAs(lncRNAs)haveemergedascriticalregulatorsofvariousbiologicalprocesses,includingcancerdevelopmentandprogression.

Inthisstudy,weidentifiedanoveloncogeniclncRNA,RP11-325L7.1,whichisupregulatedingastricadenocarcinomatissuesandcelllines.SilencingofRP11-325L7.1usingRNAinterferenceapproachinhibitedcellproliferation,migration,andinvasioningastriccancercells.Furthermore,wedemonstratedthatRP11-325L7.1promotescellmigrationandinvasionbyregulatingtheexpressionofMatrixMetalloproteinase2(MMP2),acriticalproteaseinvolvedincancermetastasis.

TheprecisemolecularmechanismsbywhichRP11-325L7.1regulatesMMP2expressionremaintobefurtherinvestigated.However,ourfindingsprovidearationaleforexploringRP11-325L7.1asanoveltherapeutictargetforgastriccancer.ThedevelopmentofspecificinhibitorstargetingRP11-325L7.1couldpotentiallyleadtothedevelopmentofmoreeffectiveandlesstoxictreatmentsforgastricadenocarcinomapatients.Inaddition,ourstudyhighlightstheimportanceoflncRNAsaspotentialbiomarkersandtherapeutictargetsincancerTheidentificationofRP11-325L7.1asapotentialtherapeutictargetforgastriccancerhighlightstheimportanceoflncRNAsincancerresearch.WiththeincreasingknowledgeonthecomplexanddiverserolesoflncRNAsincancer,thesemoleculeshaveemergedaspotentialbiomarkersandtherapeutictargetsforvarioustypesofcancers.ThedysregulatedexpressionoflncRNAshasbeenimplicatedincancerprogression,drugresistance,andmetastasis,makingthemattractivecandidatesfortargetedtherapy.

RecentadvancesintheunderstandingoflncRNAsandtheirmechanismsofactionhavepavedthewayforthedevelopmentofnewtherapeuticstrategiesforcancer.Variousapproachesarebeinginvestigated,includingtheuseofsmallmolecules,RNAinterference(RNAi)technology,andCRISPR/Cas9geneeditingtotargetlncRNAs.SmallmoleculesthatspecificallytargetlncRNAshaveshownpromiseinpreclinicalstudies,andsomehaveadvancedtoclinicaltrials.RNAi-basedtherapeuticsthattargetlncRNAsarealsobeingdeveloped,andhaveshownefficacyinpreclinicalmodelsofcancer.

Inadditiontotheirpotentialastherapeutictargets,lncRNAshavealsoshownpromiseasbiomarkersforcancerdiagnosis,prognosis,andpredictionoftherapeuticresponse.ThedysregulatedexpressionoflncRNAshasbeenobservedinvarioustypesofcancerandhasbeenassociatedwithclinicaloutcomes,includingsurvival.Furthermore,thedetectionofcirculatinglncRNAsinbloodorotherbodyfluidsholdspromiseforminimallyinvasivecancerdiagnosisandmonitoringoftreatmentresponse.

Inconclusion,theidentificationofRP11-325L7.1asapotentialtherapeutictargetforgastriccancerhighlightstheimportanceoflncRNAsincancerresearch.ThedysregulatedexpressionoflncRNAshasemergedasacommonfeatureofmultipletypesofcancer,andtheirdiverserolesincancerprogressionandmetastasismakethemattractivecandidatesfortargetedtherapy.ThedevelopmentofspecificinhibitorstargetinglncRNAs,includingRP11-325L7.1,couldpotentiallyleadtothedevelopmentofmoreeffectiveandlesstoxictreatmentsforcancerpatients.Moreover,thedetectionoflncRNAsasbiomarkersforcancerdiagnosisandprognosiscouldfacilitatepersonalizedtreatmentstrategiesandimprovepatientoutcomesLongnon-codingRNAs(lncRNAs)haveemergedasimportantplayersincancerdevelopmentandprogression.Theirdysregulationinmultipletypesofcancer,andtheirdiverserolesincancerprogressionandmetastasismakethemattractivecandidatesfortargetedtherapy.ThedevelopmentofspecificinhibitorstargetinglncRNAs,includingRP11-325L7.1,couldpotentiallyleadtothedevelopmentofmoreeffectiveandlesstoxictreatmentsforcancerpatients.Moreover,thedetectionoflncRNAsasbiomarkersforcancerdiagnosisandprognosiscouldfacilitatepersonalizedtreatmentstrategiesandimprovepatientoutcomes.

Oneofthemajorchallengesincancertreatmentistheabilityofcancercellstoadapttodifferenttherapeuticstrategies,leadingtotreatmentresistanceanddiseaserelapse.Targetedtherapiesaimedatspecificsignalingpathwayshaveshownpromisingresultsinseveralcancertypes,buttheirefficacyisoftenlimitedbytheemergenceofresistancemechanisms.OnepotentialstrategytoovercomethislimitationisthedevelopmentoftherapeuticstargetinglncRNAs,whichareinvolvedindiversecellularprocessesandcanregulatemultiplesignalingpathwayssimultaneously.

NumerousstudieshavereportedonthedysregulationoflncRNAsinvarioustypesofcancer,includingbreast,lung,prostate,andcolorectalcancer.RP11-325L7.1isanlncRNAthathasbeenimplicatedincancerdevelopmentandprogression,anditsexpressionhasbeenshowntobeassociatedwithpoorprognosisincolorectalcancerpatients.RP11-325L7.1hasalsobeenshowntopromotecancercellproliferation,migration,andinvasionbyregulatingmultiplesignalingpathways,includingtheWnt/β-cateninpathway,thePI3K/Aktpathway,andtheMAPK/ERKpathway.

TargetingRP11-325L7.1withspecificinhibitorscouldpotentiallyleadtothedevelopmentofnovelcancertreatmentswithimprovedefficacyandlowertoxicitycomparedtocurrenttherapies.ThereareseveralapproachesthatcanbeusedtodevelopinhibitorstargetinglncRNAs,includingsmallinterferingRNAs(siRNAs),antisenseoligonucleotides(ASOs),andsmallmoleculeinhibitors.SiRNAsandASOsareRNA-basedtherapeuticsthatcanspecificallytargetanddegradelncRNAs,whilesmallmoleculeinhibitorscaninhibitthefunctionoflncRNAsbyinteractingwiththeirbindingpartnersortheirfunctionaldomains.

ThedevelopmentofspecificinhibitorstargetinglncRNAs,includingRP11-325L7.1,requiresathoroughunderstandingoftheirstructure,function,andmechanismofaction.Theuseofhigh-throughputscreeningandcomputationalmodelingcanhelpidentifypotentialinhibitorswithhighspecificityandaffinityfortheirtargetlncRNAs.Theeffectivenessoftheseinhibitorscanbetestedinvitroandinvivousingcellculturesystemsandanimalmodelsofcancer.

Inadditiontotheirpotentialastherapeutictargets,lncRNAsalsohavepotentialasbiomarkersforcancerdiagnosisandprognosis.ThedysregulationoflncRNAshasbeenshowntobeassociatedwithvariousclinicalfeaturesofcancer,includingtumorsize,stage,andmetastasis.ThedetectionoflncRNAsasbiomarkersinblood,urine,orotherbodyfluidscouldfacilitateearlydetectionofcancer,monitordiseaseprogression,andpredictresponsetotreatment.

Inconclusion,lncRNAshaveemergedasimportantplayersincancerdevelopmentandprogression,providingnewopportunitiesforthedevelopmentoftargetedtherapiesandbiomarkersforcancerdiagnosisandpr