Objective:Pituitary adenomas(PAs)can adapt an aggressive phenotype by invading adjacent brain structures with rapid cellular proliferation.Previous studies demonstrated that excessive expression of metalloproteases ADAM12 and MMP-14 is instrumental for the active proliferation and invasiveness of PA cells in vitro and of tumors in vivo.However,the mechanisms regulating ADAM12 and MMP-14 expression in PAs remain unclear.Methods:Target gene prediction and transcriptomic profiling of invasive vs.noninvasive human PA samples were performed to identify miRNA species potentially involved in the regulation of ADAM12 and MMP14.For cellular analyses of miRNA functions,two mouse PA cell lines(AtT20 and TtT/GF)were transfected with miR-149-3p and miR-149-5p,respectively.The effects of miR-149(3p and 5p)on expression levels of ADAM12 and MMP14 were determined by Western blotting followed by an analysis of proliferation and colony formation assays,scratch migration assays,and invasion assays.Results:A significant downregulation of miRNA-149 was observed in invasive vs.noninvasive PA(0.32 vs.0.09,P＜0.0001).In AtT-20 and TtT/GF mouse PAs cells,transfection of mimic miRNA-149(3p and 5p)caused a significantly reduced cell proliferation and matrigel invasion,whilst the effect on cell migration was less pronounced.Both strands of miRNA-149(3p and 5p)markedly reduced protein levels of ADAM12 and MMP-14 by at least 40％in both cell lines.Conclusion:This study proved that the invasiveness of PA cells is,at least partly,regulated by miRNA-149-dependent expression of ADAM12 and MMP-14.

Zhuo ZHANG;Agnes Sch?fer;Benjamin Voellger;Jun-wen WANG;Ting LEI;Christopher Nimsky;J?rg W.Bartsch

Department of Neurosurgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Department of Neurosurgery,Philipps University Marburg,Baldingerstrasse,Marburg 35033,Germany;Sino-German Neuro-Oncology Molecular Laboratory,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Center for Mind,Brain,and Behavior,Hans-Meerwein-Strasse 6,Marburg 35032,Germany

当代医学科学(英文)

[1]Zhuo ZHANG;Agnes Sch?fer;Benjamin Voellger;Jun-wen WANG;Ting LEI;Christopher Nimsky;J?rg W.Bartsch-.MicroRNA-149 Regulates Proliferation,Migration,and Invasion of Pituitary Adenoma Cells by Targeting ADAM12 and MMP14)[J].当代医学科学(英文),2022(06):1131-1139

Regulates,Adenoma,metalloproteases,TtT

MicroRNA,Proliferation,Migration,Invasion,Pituitary,Cells,by,Targeting,ADAM12,MMP14,Objective,adenomas,PAs,adapt,aggressive,phenotype,invading,adjacent,brain,structures,rapid,cellular,proliferation,Previous,studies,demonstrated,that,excessive,expression,instrumental,active,invasiveness,cells,vitro,tumors,vivo,However,mechanisms,regulating,remain,unclear,Methods,gene,prediction,transcriptomic,profiling,noninvasive,human,samples,were,performed,identify,miRNA,species,potentially,involved,For,analyses,functions,two,mouse,lines,AtT20,GF,transfected,3p,5p,respectively,effects,levels,determined,blotting,followed,analysis,colony,formation,assays,scratch,migration,invasion,Results,downregulation,was,observed,transfection,mimic,caused,significantly,reduced,matrigel,whilst,less,pronounced,Both,strands,markedly,protein,least,both,Conclusion,This,study,proved,partly,regulated,dependent

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