miR‐199a‐5p inhibits monocyte/macrophage differentiation by targeting the activin A type 1B receptor gene and finally reducing C/EBPα expression

[摘要] miRNAsareshort,noncodingRNAsthatregulateexpressionoftargetgenesatpost‐transcriptionallevelsandfunctioninmanyimportantcellularprocesses,includingdifferentiation,proliferation,etc.Inthisstudy,weobserveddown‐regulationofmiR‐199a‐5pduringmonocyte/macrophagedifferentiationofHL‐60andTHP‐1cells,aswellashumanCD34+HSPCs.Thisdown‐regulationofmiR‐199a‐5presultedfromtheup‐regulationofPU.1thatwasdemonstratedtoregulatetranscriptionofthemiR‐199a‐2genenegatively.OverexpressionofmiR‐199a‐5pbymiR‐199a‐5pmimictransfectionorlentivirus‐mediatedgenetransfersignificantlyinhibitedmonocyte/macrophagedifferentiationofthecelllinesorHSPCs.ThemRNAencodinganACVR1BwasidentifiedasadirecttargetofmiR‐199a‐5p.GraduallyincreasedACVR1Bexpressionlevelwasdetectedduringmonocyte/macrophagedifferentiationoftheleukemiccelllinesandHSPCs,andknockdownofACVR1Bresultedininhibitionofmonocyte/macrophagedifferentiationofHL‐60andTHP‐1cells,whichsuggestedthatACVR1Bfunctionsasapositiveregulatorofmonocyte/macrophagedifferentiation.WedemonstratedthatmiR‐199a‐5poverexpressionorACVR1BknockdownpromotedproliferationofTHP‐1cellsthroughincreasingphosphorylationofRb.Wealsodemonstratedthatthedown‐regulationofACVR1Breducedp‐Smad2/3,whichresultedindecreasedexpressionofC/EBPα,akeyregulatorofmonocyte/macrophagedifferentiation,andfinally,inhibitedmonocyte/macrophagedifferentiation...

[学科分类] 生理学

[关键词] TGF‐βsignaling pathway;phosphorylation of Smad2/3;cell proliferation and cell cycle;PU.1