IncRNAHCInc1通过靶向RBBP5/KAT2B复合物增强ODC1转录促进肝癌细胞生长和转移

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Abstract：ObjectiveToinvestigatetheoleoflongnoncodingRA（ncRNA）Hlnclingulatingproliferationinasionnd migrationof hepatocellularcarcinoma （HCC）cellsand theregulatory mechanism.Methods HClnc1 expressionlevels in liver cancer tissueswere analyzed using data from the TCGA database.BrdU incorporation，plate cloning，and transwellassays were employed toexaminetheefectsof HClnc1silencing/overexpressonand/orODC1 silencingonproliferation，nvasion， andmigrationof liver cancercels.Theeffcts ofHClnc1 silencing onODC1 proteinandmRNAexpression inthelivercancer cells wereanalyzedusingqRT-PCRand Westernblotting.TheactivityofODC1promoter wasanalyzedusingadualluciferase reporter geneassy.Pul-down experiment，mass spectrometryanalysis，andchromatinimmunoprecipitation （Ch）assy wereused foridentificationof HCInc1-bindingproteins and their interactions.Proteininteractions withtheODC1promoter regionandtheirbindingeficiencieswereinvestigatedusingRNAinterferenceandChIPanalysis.ResultsHClnc1was significantlyoverexpressdinHCCtisues.Inlivercancercels，HClnclsilencingsigificantlyinhibitedcellproifeation invasion，andgtiohilecoeexpessiopromotedtseiors.DCileingasopssdliat behaviorsoflivercancercells，andcounteractedtheefectsofHClnc1overexpression.InterferenceofHClnc1obviously inhibited ODC1 promoteractivity.RBBP5and KAT2B proteins were identified tobindsimultaneously with HCInc1.HClnc1 overexpressionupregulatedODC1 protein expresson，while interference of RBBP5or KAT2Bdownregulated ODC1 protein expression and blocked HClnc1-induced upregulationof ODC1 protein.Both RBBP5and KAT2Bcould directlybind toODC1 promoter region; knockingout KAT2Bor RBBP5reduced thebinding eficiency whileknocking out HClnc1 reduced the binding of both RBBP5and KAT2B to ODC1 promoter region. Conclusion By targeting the RBBP5/KAT2B epigenetic modificationcomplex，HClnc1increasesODC1promoteractivitytoenhanceODC1transcriptionand promote theproliferation and migration of liver cancer cells.

Keywords： long noncodingRNA;hepatocellular carcinoma;RBBP5;KAT2B;ODC1; HClnc1

肝细胞癌是最常见的恶性肿瘤之一，慢性乙型/丙型肝炎感染是肝细胞癌的主要危险因素，其他危险因素还包括糖尿病、肥胖和慢性饮酒等2。（剩余15393字）