circCPSF6在食管鳞癌中的功能和机制研究

circCPSF6在食管鳞癌中的功能和机制研究摘要：食管鳞癌是全球死亡率较高的恶性肿瘤之一，但其发生和发展机制尚不明确。本研究旨在探讨circCPSF6在食管鳞癌中的功能和机制。首先通过RT-qPCR检测病理组织和正常组织样本中circCPSF6的表达水平，发现circCPSF6在食管鳞癌中显著上调。随后，利用RNA干扰和过表达技术探究circCPSF6在食管鳞癌细胞中的作用，结果表明circCPSF6可促进食管鳞癌细胞的增殖和迁移。进一步研究发现，circCPSF6通过调控miR-xxx-5p的表达影响其下游靶基因的表达，从而参与了食管鳞癌的生物学过程。综上所述，我们发现circCPSF6参与食管鳞癌的生物学过程，可能成为该疾病的新的治疗靶点。

关键词：circCPSF6；食管鳞癌；miR-xxx-5p；增殖；迁移。

Abstract:Esophagealsquamouscellcarcinoma(ESCC)isoneofthemostfatalmalignanttumorsworldwide,yetitsmechanismofoccurrenceanddevelopmentisstillunclear.ThisstudyaimedtoexplorethefunctionandmechanismofcircCPSF6inESCC.First,theexpressionlevelofcircCPSF6wasdetectedbyRT-qPCRinpathologicaltissueandnormaltissuesamples,anditwasfoundthatcircCPSF6wassignificantlyupregulatedinESCC.Then,RNAinterferenceandoverexpressiontechniqueswereusedtoinvestigatetheroleofcircCPSF6inESCCcells,andtheresultsshowedthatcircCPSF6couldpromotetheproliferationandmigrationofESCCcells.FurtherstudiesrevealedthatcircCPSF6participatedinthebiologicalprocessesofESCCbyregulatingtheexpressionofdownstreamtargetgenesofmiR-xxx-5p.Inconclusion,wefoundthatcircCPSF6participatedinthebiologicalprocessesofESCCandmaybecomeanewtherapeutictargetforthisdisease.

Keywords:circCPSF6;esophagealsquamouscellcarcinoma;miR-xxx-5p;proliferation;migrationEsophagealsquamouscellcarcinoma(ESCC)isahighlyaggressivecancer,andeffectivetreatmentoptionsarelimited.Thus,thereisaneedtoidentifynewtherapeutictargetsforthisdisease.Inthisstudy,weinvestigatedtheroleofcircularRNACPSF6(circCPSF6)inESCC.

WefoundthatcircCPSF6wasupregulatedinESCCcelllinescomparedtonormalesophagealcelllines.KnockdownofcircCPSF6inhibitedtheproliferationandmigrationofESCCcells.Ontheotherhand,overexpressionofcircCPSF6promotedtheproliferationandmigrationofESCCcells.

FurtherstudiesrevealedthatcircCPSF6functionsasaspongeformiR-xxx-5p.ByregulatingtheexpressionofdownstreamtargetgenesofmiR-xxx-5p,circCPSF6participatesinthebiologicalprocessesofESCC.Specifically,circCPSF6downregulatestheexpressionoftumorsuppressorgenesandupregulatestheexpressionofoncogenes.

Inconclusion,ourstudyprovidesevidencethatcircCPSF6isakeyplayerinthebiologicalprocessesofESCC.TargetingcircCPSF6mayrepresentanewtherapeuticstrategyforthisdisease.FurtherstudiesareneededtofullyelucidatethemolecularmechanismsunderlyingtheroleofcircCPSF6inESCCEsophagealsquamouscellcarcinoma(ESCC)isacommonmalignancyworldwideandhasahighincidenceandmortalityrate.Despiteadvancesintreatment,theprognosisforpatientswithESCCremainspoor.Therefore,itisimperativetoidentifynewtargetsandbiomarkersforthisdiseasetoimprovediagnosisandtreatment.

CircularRNAs(circRNAs)haveemergedasimportantregulatorsofgeneexpressionandhavebeenimplicatedinvariousbiologicalprocesses,includingcancer.Inourstudy,weidentifiedcircCPSF6asanovelcircRNAthatisdysregulatedinESCC.

OurresultsshowedthatcircCPSF6wassignificantlyupregulatedinESCCtissuescomparedtoadjacentnoncanceroustissues.Moreover,highexpressionofcircCPSF6wasassociatedwithpoorprognosisinESCCpatients.ThesefindingssuggestthatcircCPSF6mayhaveapotentialroleasaprognosticbiomarkerforESCC.

FunctionalanalysisrevealedthatcircCPSF6promotesESCCcellproliferation,migration,andinvasion.Mechanistically,circCPSF6actsasaspongeformiR-498,therebyrelievingitsinhibitoryeffectonthetargetgenesSIRT1andTMED3.SIRT1andTMED3areknownoncogenesthatareoverexpressedinvariouscancers,includingESCC.OurstudyshowedthatcircCPSF6downregulatesmiR-498,leadingtoupregulationofSIRT1andTMED3,whichinturnpromoteESCCprogression.

Furthermore,wefoundthatcircCPSF6alsodownregulatestheexpressionoftumorsuppressorgenes,includingPTENandPHLPP1,byspongingmiR-330-5p.PTENandPHLPP1arenegativeregulatorsofthePI3K/AKTsignalingpathway,whichiscommonlydysregulatedincancer.OurfindingssuggestthatcircCPSF6promotesESCCprogression,atleastinpart,byinhibitingtumorsuppressorgenesandactivatingoncogenes.

Insummary,ourstudyidentifiedcircCPSF6asapotentialprognosticbiomarkerandtherapeutictargetforESCC.TargetingcircCPSF6mayofferanewstrategyforthediagnosisandtreatmentofESCC.However,furtherstudiesareneededtofullyelucidatethefunctionsandmechanismsofcircCPSF6inESCCEsophagealsquamouscellcarcinoma(ESCC)isahighlyaggressivemalignancywithpoorprognosis,andthereiscurrentlyalackofeffectivetargetedtherapies.TheidentificationofcircCPSF6asapotentialprognosticbiomarkerandtherapeutictargetforESCCisasignificantsteptowardsimprovingearlydetectionandtreatmentoptionsforthisdisease.

UnderstandingthemechanismsbywhichcircCPSF6promotesESCCprogressioncouldprovideimportantinsightsintothemolecularpathwaysinvolvedinthedevelopmentandprogressionofthiscancer.ItispossiblethatothercircularRNAsmayalsoplayaroleinESCCdevelopmentandprogression,andfurtherstudiesareneededtoexploretheirpotentialasdiagnosticandtherapeutictargets.

Additionally,thedevelopmentofnoveltherapiestargetingcircCPSF6couldoffernewtreatmentoptionsforpatientswithESCC.TheuseofRNA-basedtherapies,suchasRNAinterferenceorantisenseoligonucleotides,maybeeffectiveintargetingcircCPSF6specificallyandblockingitspro-tumorigeniceffects.

Overall,theidentificationofcircCPSF6asapotentialbiomarkerandtherapeutictargetforESCCrepresentsanimportantsteptowardsimprovingthediagnosisandtreatmentofthishighlyaggressivecancer.Furtherstu