长链非编码RNA-HCG18促进肺腺癌发生发展的机制研究

长链非编码RNA-HCG18促进肺腺癌发生发展的机制研究摘要：

长链非编码RNA(lncRNA)不仅参与基因表达调控，也参与许多疾病的发生和发展。HCG18是一种新发现的lncRNA，其在多种癌症中发挥着不同的调控作用。本研究旨在阐明HCG18在肺腺癌中的表达及其调控机制，并探究其对肺腺癌发生发展的影响。结果表明，HCG18在肺腺癌中高表达，并与肺腺癌的临床分期，淋巴结转移等指标相关。HCG18过表达可以促进A549和H1299细胞的增殖和侵袭能力，并促进肿瘤的体积增大。同时，HCG18促进肿瘤免疫逃逸，在肺腺癌患者中存在较高的PD-L1表达水平。机制研究表明：HCG18与Mir-455-5p结合，抑制Mir-455-5p的表达，使得靶基因COBLL1得以表达，从而促进肺腺癌发生发展。以上结果表明HCG18在肺腺癌中具有重要的调控作用，为该疾病的治疗提供了新的思路。

关键词：长链非编码RNA，肺腺癌，HCG18，PD-L1，Mir-455-5p，COBLL1

Abstract:

Longnon-codingRNA(lncRNA)isnotonlyinvolvedingeneexpressionregulation,butalsoplaysaroleintheoccurrenceanddevelopmentofmanydiseases.HCG18isanewlydiscoveredlncRNA,whichplaysdifferentregulatoryrolesinvariouscancers.TheaimofthisstudyistoelucidatetheexpressionandregulatorymechanismofHCG18inlungadenocarcinoma,andexploreitsimpactontheoccurrenceanddevelopmentoflungadenocarcinoma.TheresultsshowedthatHCG18washighlyexpressedinlungadenocarcinomaandwasassociatedwithclinicalstaging,lymphnodemetastasisandotherindicators.OverexpressionofHCG18promotedtheproliferationandinvasionabilityofA549andH1299cells,andpromotedtumorvolumegrowth.Meanwhile,HCG18promotedtumorimmuneescape,andtherewasahighlevelofPD-L1expressioninlungadenocarcinomapatients.MechanismstudiesshowedthatHCG18boundtoMir-455-5p,inhibitedtheexpressionofMir-455-5p,andallowedthetargetgeneCOBLL1tobeexpressed,thuspromotingtheoccurrenceanddevelopmentoflungadenocarcinoma.TheaboveresultsindicatethatHCG18playsanimportantregulatoryroleinlungadenocarcinoma,providingnewideasforthetreatmentofthisdisease.

Keywords:longnon-codingRNA,lungadenocarcinoma,HCG18,PD-L1,Mir-455-5p,COBLLLungadenocarcinomaisoneofthemostcommontypesoflungcancerandoftenhasapoorprognosis.Therefore,itisnecessarytoexploretheunderlyingmechanismsofthisdiseaseandidentifypotentialtherapeutictargets.Longnon-codingRNAs(lncRNAs)havebeenshowntoplayimportantrolesinthedevelopmentandprogressionofvariouscancers,includinglungadenocarcinoma.

ThelncRNAHCG18hasbeenfoundtobeoverexpressedinlungadenocarcinomatissuesandcelllines.InvitroandinvivoexperimentsdemonstratedthatknockdownofHCG18significantlyinhibitedcellproliferation,migration,andinvasion,andinducedapoptosisinlungadenocarcinomacells.Furthermore,HCG18wasfoundtopromotetheexpressionofprogrammeddeath-ligand1(PD-L1),akeyimmunecheckpointmoleculethatisoverexpressedinmanycancers,includinglungadenocarcinoma.

MechanismstudiesshowedthatHCG18boundtoMir-455-5p,amicroRNAthathasbeenshowntohavetumor-suppressivefunctionsinvariouscancers,andinhibiteditsexpression.ThissuppressionofMir-455-5pallowedthetargetgeneCOBLL1tobeexpressed,thuspromotingtheoccurrenceanddevelopmentoflungadenocarcinoma.ThesefindingssuggestthatHCG18mayactasanoncogeniclncRNAinlungadenocarcinomabyregulatingtheMir-455-5p/COBLL1axis.

Inconclusion,HCG18playsanimportantregulatoryroleinlungadenocarcinomabypromotingcellproliferation,invasion,andPD-L1expressionthroughtheregulationoftheMir-455-5p/COBLL1axis.TheseresultsprovidenewinsightsintothepathogenesisoflungadenocarcinomaandmaycontributetothedevelopmentofnoveltherapeuticstrategiesforthisdiseaseInadditiontoitsregulatoryroleinlungadenocarcinoma,HCG18hasalsobeenshowntobeinvolvedinthedevelopmentandprogressionofothertypesofcancer,includinggastriccancerandcolorectalcancer.ThishighlightsthepotentialsignificanceofHCG18asatherapeutictargetformultipletypesofcancer.

Furthermore,theMir-455-5p/COBLL1axis,whichisregulatedbyHCG18,mayalsohavebroaderimplicationsincancerbiology.Mir-455-5phasbeenreportedtobedysregulatedinmultipletypesofcancerandhasbeenshowntoplayaroleintumorgrowth,invasion,andmetastasis.COBLL1,atargetofMir-455-5p,hasalsobeenimplicatedintumorgrowthandmetastasisinbothlungcancerandbreastcancer.Thus,targetingthisaxismayhavebroadtherapeuticpotential.

Inconclusion,theidentificationandcharacterizationofHCG18asaregulatoroftheMir-455-5p/COBLL1axisinlungadenocarcinomaprovidesnewinsightsintothepathogenesisofthisdiseaseandmayleadtothedevelopmentofnoveltherapeuticstrategies.FurtherresearchisneededtofullyunderstandtheroleofHCG18incancerbiologyandtoexploreitspotentialasatherapeutictargetinothertypesofcancerLungadenocarcinomaisacomplexdiseasewithmultiplemolecularsubtypesandahighdegreeofheterogeneity.Despiteadvancesintreatmentoptions,theprognosisforpatientswithadvancedlungadenocarcinomaremainspoor.ThediscoveryofHCG18asaregulatoroftheMir-455-5p/COBLL1axisinlungadenocarcinomaoffersnewhopeforthedevelopmentoftargetedtherapies.

FurtherresearchisneededtofullyunderstandthemechanismsbywhichHCG18regulatestheMir-455-5p/COBLL1axisandhowthispathwaycontributestothedevelopmentandprogressionoflungadenocarcinoma.ItwillalsobeimportanttodeterminewhetherHCG18playsasimilarroleinothertypesofcancer.

Inadditiontoitspotentialasatherapeutictarget,HCG18mayalsohavediagnosticvalue.ElevatedlevelsofHCG18inserumortissuesamplescouldserveasabiomarkerforlungadenocarcinomaandothercancers.

ThediscoveryofHCG18asaregulatoroftheMir-455-5p/COBLL1axisunderscorestheimportanceofnon-codingRNAsincancerbiology.AsmoreislearnedaboutthefunctionsoftheseRNAs,newtherapeutictargetsanddiagnosticbiomarkerswillundoubtedlybeidentified.

Inconclusion,theidentificationandcharacterizationofHCG18asaregulatoroftheMir-455-5p/COBLL1axisinlungadenocarcinomarepresentsanimportantadvanceinourunderstandingofthiscomplexdisea