MicroRNA--126在三氧化二砷抑制人脐静脉内皮细胞中的作用机制的开题报告Title:MechanismofMicroRNA-126SuppressioninArsenicTrioxideInhibitedHumanUmbilicalVeinEndothelialCellsBackground:Arsenictrioxide(ATO)isachemotherapeuticagentthathasbeenusedforthetreatmentofvarioustypesofcancers,includingacutepromyelocyticleukemiaandsolidtumors.However,theuseofATOisassociatedwithseveralsideeffects,includingcardiovasculartoxicity.IthasbeenshownthatATOcaninhibittheproliferationandmigrationofhumanumbilicalveinendothelialcells(HUVECs),whichareimportantinmaintainingvascularhomeostasis.MicroRNA-126(miR-126)hasbeenimplicatedinregulatingthefunctionofendothelialcellsandisdownregulatedinvariouspathologies,suchasatherosclerosisandcancer.TheroleofmiR-126inATO-treatedHUVECsremainsunclear.Objective:OurobjectiveistoinvestigatethemechanismbywhichmiR-126issuppressedinATO-treatedHUVECs.Methods:WewilltreatHUVECswithdifferentconcentrationsofATOandevaluatetheexpressionofmiR-126usingqRT-PCR.WesternblottingwillbeperformedtoassessthelevelsofproteinsinvolvedinthemiR-126pathway,suchasvascularendothelialgrowthfactor-A(VEGF-A)andp85αregulatorysubunitofphosphatidylinositol3-kinase(PI3K).ThebindingofmiR-126toitstargetgeneswillbedeterminedusingluciferasereporterassays.CellproliferationandmigrationassayswillalsobeperformedtoevaluatetheeffectsofmiR-126suppressiononthefunctionofHUVECs.Expectedresults:WeexpecttoobserveadownregulationofmiR-126inATO-treatedHUVECs,whichmaybeduetotheinhibitionofVEGF-AandPI3Kexpression.WealsoexpecttodemonstratethatmiR-126canregulatetheproliferationandmigrationofHUVECs,andthatthesuppressionofmiR-126maycontributetotheanti-proliferativeandanti-migratoryeffectsofATOonHUVECs.Significance:ThisstudywillprovideinsightsintothemechanismbywhichATOaffectsthefunctionofendothelialcellsandmayidentifymiR-126asapotentialtherapeutictargetforreducingthecardiovasculartoxicityofATOtreatment.