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CASP8AP2与ZEB2 - CtBP2之间的相互作用调节……的表达。 (原文此处不完整,缺少具体被调节表达的内容)

Interaction between CASP8AP2 and ZEB2-CtBP2 Regulates the Expression of .

作者信息

Wang Chan-Juan, Jia Ming-Zhu, Deng Li-Ping, Li Wei-Jing, Zhang Qing, Zhang Tong-Jia, Li Shu-Yan, Cui Lei, Li Zhi-Gang

机构信息

Hematologic Diseases Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.

出版信息

Pediatr Hematol Oncol. 2022 Sep;39(6):549-560. doi: 10.1080/08880018.2022.2033369. Epub 2022 Feb 10.

Abstract

Low expression of and correlated with poor outcome and predicted risk of relapse in pediatric B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to investigate the molecular mechanism by which CASP8AP2 regulates LEF1 expression by interacting with CtBP2 and ZEB2 in Acute lymphoblastic lymphoma (ALL). There was an interaction between CASP8AP2, ZEB2, and CtBP2, and then the interaction between CtBP2 and ZEB2 was observed after downregulating the expression of CASP8AP2. The wild type (containing the ZEB2 binding site) or mutant (containing a mutant binding site) gene promoter sequence was inserted into the pGL3-basic plasmid, and a dual-luciferase reporter gene detection system was used to observe how CASP8AP2, ZEB2, and CtBP2 regulate the transcription of the gene. We conclude that CASP8AP2, CtBP2, and ZEB2 can all bind to the gene promoter region and reduce the luciferase activity of the promoter. Meanwhile, the interaction of ZEB2 and the promoter was significantly weakened after downregulation of CASP8AP2. Knockdown of CASP8AP2 in the 697 cell lines resulted in the significant upregulation of the mRNA expression levels of the stemness-related genes , , and . In conclusion, CASP8AP2 is vital for the interaction between CtBP2 and ZEB2, inhibiting LEF1 and stemness-related genes expression ALL.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2033369 .

摘要

在儿童B细胞急性淋巴细胞白血病(B-ALL)中, 和 的低表达与不良预后相关,并预测复发风险。本研究旨在探讨在急性淋巴细胞淋巴瘤(ALL)中,CASP8AP2通过与CtBP2和ZEB2相互作用调节LEF1表达的分子机制。CASP8AP2、ZEB2和CtBP2之间存在相互作用,下调CASP8AP2表达后观察到CtBP2和ZEB2之间的相互作用。将野生型(含ZEB2结合位点)或突变型(含突变结合位点) 基因启动子序列插入pGL3-basic质粒,使用双荧光素酶报告基因检测系统观察CASP8AP2、ZEB2和CtBP2如何调节 基因的转录。我们得出结论,CASP8AP2、CtBP2和ZEB2均可与 基因启动子区域结合并降低 启动子的荧光素酶活性。同时,下调CASP8AP2后,ZEB2与 启动子的相互作用显著减弱。在697细胞系中敲低CASP8AP2导致干性相关基因 、 和 的mRNA表达水平显著上调。总之,CASP8AP2对CtBP2和ZEB2之间的相互作用至关重要,可抑制ALL中LEF1和干性相关基因的表达。本文的补充数据可在网上获取,网址为https://doi.org/10.1080/08880018.2022.2033369

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