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tenantId=1146029695717560320, journalId=1315121837170065538, language=CN, title=马归液靶向转录因子-miRNA反馈环抗膀胱癌的机制研究, columnId=null, journalTitle=中医学报, columnName=实验研究, runingTitle=null, highlight=null, articleAbstract=目的:探讨马归液通过靶向转录因子激活蛋白2A(Transcription Factor Activating Protein 2 Alpha,TFAP2A)-微小RNA(microRNA,miRNA)反馈环抑制膀胱癌的作用机制。方法:制备不同浓度马归液含药血清。以人膀胱癌T24细胞为研究对象，设空白血清对照组、不同浓度马归液含药血清组及TFAP2A过表达组。采用CCK-8法、Transwell实验和Annexin VAPC/PI流式细胞术检测细胞增殖、迁移与凋亡;采用基因芯片技术筛选差异表达基因并进行基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析;基于TCGA数据库筛选膀胱癌差异表达miRNA，通过FunRich、TransmiR等数据库构建并验证TF-miRNA反馈调控网络;采用蛋白质免疫印迹(Western blot)法和实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)法检测关键分子表达。结果:与空白对照组对比，马归液含药血清能显著抑制T24细胞增殖与迁移，并促进其凋亡(均P<0.05)，且呈浓度依赖性。基因芯片筛选出1856个差异表达mRNA,KEGG富集于MAPK、PI3K-Akt等信号通路。生物信息学分析构建出以TFAP2A为核心，包含miR-135b、miR-455的反馈环;临床数据分析显示TFAP2A在膀胱癌组织中高表达且与不良预后相关(P<0.05)。功能实验证实，过表达TFAP2A可促进膀胱癌细胞增殖并抑制凋亡(P<0.05)。与模型组对比，马归液含药血清可显著下调TFAP2A的mRNA和蛋白表达水平(P<0.05)，且抑制作用呈浓度依赖性。结论:马归液可能通过靶向TFAP2A-miRNA(miR-135b、miR-455)反馈环，抑制膀胱癌细胞增殖与迁移，并诱导其凋亡，从而发挥抗膀胱癌作用。, authors=null, authorsList=null, authorCompany=null, correspAuthors=null, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null)}, authors=[Author(id=1319955819253314386, tenantId=1146029695717560320, journalId=1315121837170065538, 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