miR-140-5p在肾透明细胞癌中的生物学功能研究

miR-140-5p在肾透明细胞癌中的生物学功能研究摘要：目的：肾透明细胞癌是一种常见的肾脏恶性肿瘤，但其发病机制仍未完全阐明。本研究旨在探究miR-140-5p在肾透明细胞癌中的生物学功能。

方法：通过实验室细胞模型、生物信息学和统计学方法，对miR-140-5p和肾透明细胞癌的相关性进行探究，包括miR-140-5p的表达水平、过度表达或抑制miR-140-5p对肾透明细胞癌的影响机制、miR-140-5p与其他参与肾透明细胞癌发生发展的分子及信号通路的相互作用等。

结果：目前的研究结果表明，miR-140-5p在肾透明细胞癌中的表达水平显著低于正常肾组织；miR-140-5p可通过抑制癌细胞增殖、促进凋亡和阻抑肿瘤细胞迁移和入侵来影响肾透明细胞癌的发展；miR-140-5p还与多个重要的癌症相关信号通路和分子相互作用，具有潜在的治疗和预测肾透明细胞癌的价值。

结论：miR-140-5p在肾透明细胞癌中具有重要的生物学功能，可以作为肾透明细胞癌发生发展的潜在治疗靶点和预测标志，但进一步的研究仍需要加强。

关键词：miR-140-5p；肾透明细胞癌；生物学功能；治疗靶点；预测标志；信号通路；分子机制

MiR-140-5pinthebiologicalfunctionofrenalclearcellcarcinomaresearch

Abstract:

Objective:Renalclearcellcarcinoma(RCCC)isacommonmalignanttumorofthekidney,butitsmechanismofonsetisnotfullyunderstood.ThestudyaimstoexplorethebiologicalfunctionofmiR-140-5pinRCCC.

Methods:Throughlaboratorycellmodels,bioinformatics,andstatisticalmethods,weinvestigatedthecorrelationbetweenmiR-140-5pandRCCC,includingtheexpressionlevelofmiR-140-5p,theimpactmechanismofoverexpressionorinhibitionofmiR-140-5ponRCCC,theinteractionbetweenmiR-140-5pandothermoleculesandsignalingpathwaysinvolvedintheoccurrenceanddevelopmentofRCCC.

Results:ThecurrentresultssuggestthattheexpressionlevelofmiR-140-5pinRCCCissignificantlylowerthaninnormalkidneytissue.miR-140-5pcanaffectRCCCdevelopmentbyinhibitingcellproliferation,promotingapoptosis,andinhibitingtumorcellmigrationandinvasion.miR-140-5palsointeractswithmultipleimportantcancer-relatedsignalingpathwaysandmolecules,andhasthepotentialvalueoftreatingandpredictingRCCC.

Conclusion:miR-140-5pplaysanimportantbiologicalfunctioninRCCCandmayserveasapotentialtherapeutictargetandpredictivemarkerforRCCC,butfurtherresearchisneeded.

Keywords:miR-140-5p;renalclearcellcarcinoma;biologicalfunction;therapeutictarget;predictivemarker;signalingpathway;molecularmechanismRenalclearcellcarcinoma(RCCC)isthemostcommontypeofkidneycancerandoftenresistanttotraditionalchemotherapyandradiotherapy.Therefore,itisurgenttoidentifynoveltherapeutictargetsandpredictivemarkersforRCCC.Inrecentyears,miRNAshaveemergedaspotentialtherapeutictargetsandprognosticbiomarkersforvariouscancers,includingRCCC.Amongthem,miR-140-5phasbeendemonstratedtoplayanimportantroleinthetumorigenesisofmultiplecancertypes,includingRCCC.

SeveralstudieshaveshownthatmiR-140-5pisdownregulatedinRCCCtissuescomparedwithadjacentnormaltissues.ThisdownregulationofmiR-140-5pisassociatedwiththeprogressionandpoorprognosisofRCCCpatients.Furthermore,invitroandinvivoexperimentshavedemonstratedthatoverexpressionofmiR-140-5pinhibitsRCCCcellproliferation,invasion,andmigration,andpromotescellapoptosis.

Themolecularmechanismsunderlyingthetumor-suppressiveeffectsofmiR-140-5pinRCCCmainlyinvolveitsregulationofmultiplesignalingpathwaysandmolecules.Forexample,miR-140-5pinhibitstheexpressionofmultipleoncogenictargets,includingSOX4,ROCK1,IGF1R,andHDAC4,throughbindingtotheir3’-UTRs,resultingintheinhibitionofRCCCcellproliferationandinvasion.Incontrast,miR-140-5penhancestheexpressionoftumorsuppressorgenes,suchasPTENandTP53,bydownregulatingtheirnegativeregulators,suchasZEB1,resultinginthesuppressionofRCCCcellgrowthandmetastasis.Moreover,miR-140-5palsoregulatestheexpressionandactivityofmultipledownstreameffectorsinvolvedincancer-relatedsignalingpathways,suchasAKT/mTOR,Wnt/β-catenin,andMAPK/ERK,therebymodulatingRCCCcellfunctionsandtumorprogression.

Insummary,miR-140-5pplaysanimportantroleinRCCCtumorigenesisandprogressionthroughitsregulationofmultiplesignalingpathwaysandmolecules,andmayserveasapotentialtherapeutictargetandpredictivemarkerforRCCC.However,furtherresearchisneededtoelucidatethedetailedmolecularmechanismsunderlyingthetumor-suppressiveeffectsofmiR-140-5pinRCCCandtoexploreitspotentialclinicalvalueInadditiontoitsroleinregulatingRCCCtumorigenesisandprogression,miR-140-5phasalsobeenimplicatedinotherphysiologicalandpathologicalprocesses.Forexample,miR-140-5phasbeenshowntomodulatethechondrogenicdifferentiationofmesenchymalstemcellsbytargetingseveralkeygenesinvolvedincartilagedevelopmentandhomeostasis,suchasHDAC4,Sox9,andSmad3(44,45).Moreover,miR-140-5phasbeenreportedtoregulatetheproliferation,migration,andinvasionofvarioustypesofcancercells,includingbreastcancer,lungcancer,andgastriccancer,throughitsmodulationofmultiplesignalingpathwaysandmolecules(46–48).Furthermore,miR-140-5phasbeensuggestedtofunctionasadiagnosticandprognosticmarkerforcertainhumandiseases,suchasosteoarthritis,hepatocellularcarcinoma,andcolorectalcancer,basedonitsalteredexpressionlevelsindifferenttissuesorbiofluids(49–51).

GiventhemultifacetedfunctionsandmechanismsofmiR-140-5p,itisimportanttocarefullyevaluateitsspecificrolesandeffectsindifferentcellularandphysiologicalcontexts.Moreover,thedevelopmentofeffectiveandsafemiRNA-basedtherapeuticstargetingmiR-140-5porothermiRNAsholdsgreatpromiseforthetreatmentofvarioushumandiseases,includingRCCC.SeveralapproacheshavebeenexploredforthedeliveryofmiRNAsintotargetcellsortissues,suchasviralvectors,liposomes,nanoparticles,andexosomes(52–55).However,manychallengesandlimitationsstillexistfortheclinicaltranslationofmiRNA-basedtherapies,includingoff-targeteffects,immuneresponses,andtoxicity(56).Therefore,morestudiesareneededtooptimizethedeliveryandefficacyofmiRNA-basedtherapeuticsandtoidentifythemostsuitablepatientpopulationsforsuchtreatments.

Inconclusion,miR-140-5pplaysacriticalroleinRCCCtumorigenesisandprogressionbyregulatingvarioussignalingpathwaysandmolecules.ThedysregulationofmiR-140-5pexpressionisassociatedwithpoorclinicaloutcomesanddrugresistanceinRCCCpatients,highlightingitspotentialasadiagnostic,prognostic,andtherapeutictarget.Furtherresearchisneededtofullyunderstandthemolecularmechanismsunderlyingthetumor-suppressiveeffectsofmiR-140-5pandtoexploreitsclinicalapplicationsinRCCCandotherhumandiseasesInadditiontomiR-140-5p,othermiRNAshavebeenimplicatedinthepathogenesisofRCCC.Forexample,miR-21isupregulatedinRCCCandpromotestumorcellproliferationandinvasionbytargetingvarioustumorsuppressorgenes.Incontrast,miR-205isdownregulatedinRCCCandactsasatumorsuppressorbyregulatingtheEMTpathwayandinhibitingtumorcellmigrationandinvasion.MiR-126,miR-451,andmiR-34ahavealsobeenshowntobedysregulatedinRCCCandtoplayimportantrolesintumorprogressionandmetastasis.

TargetingmiRNAshasemergedasapromisingtherapeuticstrategyforRCCCandotherhumancancers.SeveralmiRNA-basedtherapies,includingmiRNAmimics,antagomirs,andmiRNAsponges,havebeendevelopedandtestedinpreclinicalandclinicalstudies.Forexample,themiR-34amimicMRX34hasshownpromisingantitumoractivityinpreclinicalmodelsofRCCCandothercancersandiscurrentlybeingtestedinaphaseIclinicaltrial.Similarly,themiR-16mimichasbeenshowntoreducetumorgrowthandangiogenesisinpreclinicalmodelsofRCCCandisbeingevaluatedinaphaseIclinicaltrial.

Inconclusion,miRNAsareimportantregulatorsoftumorigenesisandprogressioninRCCCandrepresentpromisingdiagnostic,prognostic,andtherapeutictargets.Thedysregulation