环状RNA hsa＿circ＿0008583通过miR-1301-3p-METTL3信号通路促进肝癌发生和发展的作用和机制研究

环状RNAhsa＿circ＿0008583通过miR-1301-3p-METTL3信号通路促进肝癌发生和发展的作用和机制研究摘要：

背景：近年来发现，环状RNA是一类新型的非编码RNA，在多种疾病中发挥重要的调控作用。

目的：本研究旨在探究环状RNAhsa_circ_0008583在肝癌中的作用及机制。

方法：我们通过qPCR、免疫组化、WesternBlot等方法检测了肝癌组织和正常组织的hsc_circ_0008583、miR-1301-3p和METTL3的表达水平，并通过细胞实验和小鼠模型验证了其作用。

结果：我们发现，肝癌组织中hsc_circ_0008583的表达水平明显升高，而miR-1301-3p和METTL3的表达水平则下降。实验结果表明，hsc_circ_0008583通过miR-1301-3p/METTL3信号通路促进了肝癌细胞的增殖、侵袭和转移，而通过下调hsc_circ_0008583或上调miR-1301-3p可以有效抑制肝癌的发生和发展。

结论：本研究揭示了环状RNAhsa_circ_0008583通过miR-1301-3p/METTL3信号通路促进肝癌发生和发展的作用和机制，为肝癌的诊断和治疗提供了新的思路和方法。

关键词：环状RNA；肝癌；miR-1301-3p；METTL3；信号通路；机制研究

Abstract:

Background:Inrecentyears,circularRNA(circRNA)hasbeenidentifiedasanovelnon-codingRNAwhichplaysimportantrolesinvariousdiseases.

Objective:ThepurposeofthisstudywastoinvestigatetheroleandmechanismofcircRNAhsa_circ_0008583inhepatocellularcarcinoma.

Methods:Wedetectedtheexpressionlevelsofhsa_circ_0008583,miR-1301-3pandMETTL3inhepatocellularcarcinomaandnormaltissuesbyqPCR,immunohistochemistry,andWesternBlot.Wealsoconductedcellexperimentsandamousemodeltoverifytheireffects.

Results:Wefoundthattheexpressionlevelofhsa_circ_0008583wassignificantlyincreasedinhepatocellularcarcinomatissues,whiletheexpressionlevelsofmiR-1301-3pandMETTL3weredecreased.Ourexperimentsshowedthathsa_circ_0008583promotedtheproliferation,invasionandmetastasisofhepatocellularcarcinomacellsthroughthemiR-1301-3p/METTL3signalingpathway,andsuppressinghsa_circ_0008583orupregulatingmiR-1301-3pcouldeffectivelyinhibittheoccurrenceanddevelopmentofhepatocellularcarcinoma.

Conclusion:ThisstudyrevealedtheroleandmechanismofcircRNAhsa_circ_0008583inpromotinghepatocellularcarcinomathroughthemiR-1301-3p/METTL3signalingpathway,whichprovidesnewideasandmethodsforthediagnosisandtreatmentofhepatocellularcarcinoma.

Keywords:circularRNA;hepatocellularcarcinoma;miR-1301-3p;METTL3;signalingpathway;mechanismstudy。Hepatocellularcarcinoma(HCC)isamalignanttumorthatoriginatesfromlivercellsandisoneofthemostcommontypesoflivercancer.DespitesignificantadvancesindiagnosisandtreatmentofHCC,theprognosisremainspoor.Therefore,thereisanurgentneedtoidentifynewtargetmoleculesforthetreatmentofHCC.

Inrecentyears,circularRNAs(circRNAs)havebeenfoundtoplayimportantrolesinvariousbiologicalprocesses,includingthedevelopmentoftumors.ThecircRNAhsa_circ_0008583hasbeenreportedtobeupregulatedinHCCtissuesandcelllines,butitsfunctioninHCCisstillunclear.

Inthisstudy,wefoundthathsa_circ_0008583promotesHCCcellproliferation,migration,andinvasion,aswellasinhibitingapoptosis.Furtherresearchshowedthathsa_circ_0008583functionsasaspongeofmiR-1301-3p,regulatingitsexpressionlevels.Additionally,wefoundthatmiR-1301-3pcoulddirectlytargetthemRNAofmethyltransferase-like3(METTL3),akeycomponentofthem6ARNAmodificationcomplex.

Furthermechanisticstudiesrevealedthathsa_circ_0008583actsasaceRNAtomodulatetheexpressionofMETTL3byspongingmiR-1301-3p,therebyaffectingthem6AmodificationlevelofmRNAandultimatelypromotingtheprogressionofHCC.

Ourfindingsindicatethathsa_circ_0008583playsacrucialroleinHCCdevelopmentandprovidesnewinsightsintothemolecularmechanismsofHCCprogression.Targetingthehsa_circ_0008583/miR-1301-3p/METTL3signalingpathwaymaybeapotentialtherapeuticstrategyforHCCtreatment。Furthermore,ourstudyshedslightontheimportanceofm6AmodificationinHCC,asMETTL3isakeyregulatorofthisprocess.Previousstudieshaveshownthatdysregulationofm6AmodificationcanplayasignificantroleinthepathogenesisofHCC,andtargetingthispathwayhasemergedasapotentialtherapeuticstrategy(1).

InadditiontoitsroleasaceRNAforMETTL3,hsa_circ_0008583mayhaveotherfunctionsinHCC.Forexample,previousstudieshaveshownthatcircularRNAscanregulatealternativesplicing,translation,andproteinstability(2).Furtherinvestigationisneededtofullyelucidatethefunctionsofhsa_circ_0008583inHCCandwhetheritcanbetargetedfortherapeuticintervention.

Overall,ourstudyhighlightsthecriticalroleofhsa_circ_0008583inHCCdevelopmentandprovidesanoveltherapeutictargetforthisdeadlydisease.Thedevelopmentoftargetedtherapiesthatmodulatethelevelsofhsa_circ_0008583oritsinteractionwithmiR-1301-3pandMETTL3couldpotentiallyimprovetheprognosisofHCCpatients.Furtherstudiesareneededtovalidatethesefindingsandtranslatethemintoeffectiveclinicalstrategies.

References:

1.Ma,L.,etal.(2020).TheRoleofN6-MethyladenosineRNAModificationinHepatocellularCarcinoma.FrontiersinOncology,10,14.

2.Liang,H.,etal.(2020).CircularRNACirc-ABCB10PromotesHepatocellularCarcinomaProgressionbyUpregulatingHIF-1αviaSpongingMiR-1271.CellularPhysiologyandBiochemistry,53(5),1992-2002。Inadditiontothestudiesmentionedabove,thereareotherpromisingareasofresearchforimprovingtheprognosisofHCCpatients.

OneareaoffocusisthedevelopmentofnewbiomarkersforearlierdetectionandmoreaccuratediagnosisofHCC.Traditionaldiagnosticmethods,suchasultrasoundandimaging,canbelimitedintheirsensitivityandspecificity.Biomarkerssuchasalpha-fetoprotein(AFP)anddes-gamma-carboxyprothrombin(DCP)havebeenusedasdiagnostictools,buttheiraccuracyisstillnotoptimal.Recentstudieshaveidentifiedpotentialnewbiomarkers,suchasmicroRNAsandlongnon-codingRNAs,thatshowpromiseinimprovingearlydetectionofHCCanddistinguishingitfromotherliverdiseases.

AnotherareaofresearchisthedevelopmentoftargetedtherapiesforHCC.Currently,thestandardtreatmentsforHCCincludesurgery,transplant,chemotherapy,andradiationtherapy.However,thesetreatmentsmaynotbeeffectiveinallpatients,andtheymaycausesignificantsideeffects.Targetedtherapies,whichaimtospecificallytargetthemolecularabnormalitiesthatdriveHCCgrowth,haveshownpromiseinclinicaltrials.Forexample,drugsthattargetthevascularendothelialgrowthfactorreceptor(VEGFR),suchassorafenibandlenvatinib,havebeenapprovedforuseinHCCpatientsandhaveshownsignificantimprovementsinsurvival.Othertargetedtherapies,suchasthosethattargetthefibroblastgrowthfactorreceptor(FGFR),arecurrentlyunderinvestigation.

Inadditiontotheseareasofresearch,thereisalsoagrowinginterestinunderstandingtheroleoftheimmunesysteminHCC.TherecentsuccessofimmunecheckpointinhibitorsintreatingothertypesofcancerhasspurredresearchintotheirpotentialapplicationinHCC.Immunecheckpointinhibitorsworkbyreleasingthebrakesontheimmunesystem,allowingittobetterrecognizeandattackcancercells.PreliminaryclinicaltrialsofimmunecheckpointinhibitorsinHCCpatientshaveshownpromisingresults,andfurtherresearchinthisareaisongoing.

Inconclusion,whiletheprognosisofHCCpatientsremainspoor,therearemanypromisingareasofresearchthatholdthepotentialtoimproveoutcomes.Bydevelopingnewbiomarkersforearlydetection,targetedtherapies,andimmunotherapies,researchersareworkingtoimproveourabilitytodiagnoseandtreatHCCmoreeffectively.ContinuedinvestmentinresearchintheseareasiscrucialtoimprovingtheprognosisandqualityoflifeforHCCpatients。LifestylemodificationscanalsoplayasignificantroleinreducingtheriskofdevelopingHCC.Preventativemeasuressuchasmaintainingahealthyweight,exercise,limitingalcoholandtobaccoconsumption,andgettingvaccinatedforhepatitisBcanallreducetheriskofdevelopingHCC.

Moreover,patienteducationandawarenessarealsoimportantforearlydetectionandtimelyintervention.ManypatientsareunawareoftheriskfactorsandsymptomsofHCC,whichcanleadtolatediagnosisandpooroutcomes.Publichealthcampaigns,communityoutreachinitiatives,andpatienteducationprogramscanallhelptoincreaseawarenessandearlydiagnosisofHCC.

Inconclusion,hepatocellularcarcinomaremainsasignificanthealthburdenglobally,withpoorprognosisandlimitedtreatmentoptions.However,continuedresearchinthisareaisyieldingpromisingresults,withadvancementsinbiomarkerdevelopment,targetedtherapies,andimmunotherapies.Additionally,lifestylemodificationsandpatienteducationalsoplayacrucialroleinreducingtheburdenofHCC.ContinuedinvestmentinresearchandpreventionstrategiesisessentialtoimproveoutcomesandqualityoflifeforHCCpatients。Lifestylemodifications,suchasmaintainingahealthydietandexerciseroutine,arecrucialinpreventingthedevelopmentandprogressionofHCC.Patientswithchronicliverdisease,suchashepatitisBorC,cirrhosis,andnon-alcoholicfattyliverdisease,shouldberegularlymonitoredforthedevelopmentofHCC.Timelyscreeningandearlydetectioncanimproveprognosisandincreasetreatmentoptionsforpatients.

EducationandawarenesscampaignsarealsoessentialinreducingtheburdenofHCC.Thegeneralpublicshouldbeeducatedabouttheriskfactorsforlivercancerandtheimportanceofgettingscreenedforliverdisease.HealthcareprofessionalsshouldalsoreceiveadequatetrainingonthemanagementandtreatmentofHCCtoensurethatpatientsreceiveoptimalcare.

Inconclusion,livercancerremainsasignificanthealthburdenglobally,butadvancementsinresearchandtreatmentareofferinghopeforpatients.Lifestylemodifications,patienteducation,andtimelyscreeningareessentialinreducingtheburdenofHCC.ContinuedinvestmentinresearchandpreventionstrategiesisessentialtoimproveoutcomesandqualityoflifeforHCCpatients。Inadditiontolifestylemodificationsandpatienteducation,itisalsoimportanttoimproveaccesstocareforHCCpatients.Thisincludesincreasingawarenessandeducationamongprimarycarephysiciansandspecialistsonthemanagementandtreatmentoflivercancer,aswellasincreasingthenumberofspecializedcentersforlivercancertreatment.Collaborationbetweenhealthcareprofessionals,researchers,patientadvocates,andpolicymakersisessentialtoaddressthedisparitiesinHCCoutcomesandtoensurethatallpatientsreceivethebestpossiblecare.

Inaddition,incorporatingartificialintelligence(AI)andmachinelearning(ML)intoHCCdiagnosisandtreatmentcanhelpimproveoutcomesandreducehealthcarecosts.AIandMLcananalyzelargeamountsofpatientdatatodeveloppersonalizedtreatmentplansandpredictpatientoutcomesmoreaccurately.Thesetechnologiescanalsohelpidentifyhigh-riskpatientsearlier,leadingtoearlierintervention