miR-140-5p在腎透明細(xì)胞癌中的生物學(xué)功能研究

miR-140-5p在腎透明細(xì)胞癌中的生物學(xué)功能研究摘要：目的：腎透明細(xì)胞癌是一種常見的腎臟惡性腫瘤，但其發(fā)病機(jī)制仍未完全闡明。本研究旨在探究miR-140-5p在腎透明細(xì)胞癌中的生物學(xué)功能。

方法：通過實(shí)驗(yàn)室細(xì)胞模型、生物信息學(xué)和統(tǒng)計(jì)學(xué)方法，對miR-140-5p和腎透明細(xì)胞癌的相關(guān)性進(jìn)行探究，包括miR-140-5p的表達(dá)水平、過度表達(dá)或抑制miR-140-5p對腎透明細(xì)胞癌的影響機(jī)制、miR-140-5p與其他參與腎透明細(xì)胞癌發(fā)生發(fā)展的分子及信號通路的相互作用等。

結(jié)果：目前的研究結(jié)果表明，miR-140-5p在腎透明細(xì)胞癌中的表達(dá)水平顯著低于正常腎組織；miR-140-5p可通過抑制癌細(xì)胞增殖、促進(jìn)凋亡和阻抑腫瘤細(xì)胞遷移和入侵來影響腎透明細(xì)胞癌的發(fā)展；miR-140-5p還與多個(gè)重要的癌癥相關(guān)信號通路和分子相互作用，具有潛在的治療和預(yù)測腎透明細(xì)胞癌的價(jià)值。

結(jié)論：miR-140-5p在腎透明細(xì)胞癌中具有重要的生物學(xué)功能，可以作為腎透明細(xì)胞癌發(fā)生發(fā)展的潛在治療靶點(diǎn)和預(yù)測標(biāo)志，但進(jìn)一步的研究仍需要加強(qiáng)。

關(guān)鍵詞：miR-140-5p；腎透明細(xì)胞癌；生物學(xué)功能；治療靶點(diǎn)；預(yù)測標(biāo)志；信號通路；分子機(jī)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