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Interaction between CASP8AP2 and ZEB2-CtBP2 Regulates the Expression of LEF1
Pediatric Hematology and Oncology ( IF 1.7 ) Pub Date : 2022-02-10 , DOI: 10.1080/08880018.2022.2033369
Chan-Juan Wang 1 , Ming-Zhu Jia 1 , Li-Ping Deng 2 , Wei-Jing Li 1 , Qing Zhang 1 , Tong-Jia Zhang 3 , Shu-Yan Li 3 , Lei Cui 1 , Zhi-Gang Li 1
Affiliation  

Abstract

Low expression of CTBP2 and CASP8AP2 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) LEF1 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 LEF1 gene. We conclude that CASP8AP2, CtBP2, and ZEB2 can all bind to the LEF1 gene promoter region and reduce the luciferase activity of the LEF1 promoter. Meanwhile, the interaction of ZEB2 and the LEF1 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 CD44, JAG1, and SALL4. 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 .



中文翻译:

CASP8AP2 和 ZEB2-CtBP2 之间的相互作用调节 LEF1 的表达

摘要

CTBP2CASP8AP2的低表达与小儿 B 细胞急性淋巴细胞白血病 (B-ALL) 的不良结果和预测的复发风险相关。本研究旨在探讨 CA​​SP8AP2 通过与 CtBP2 和 ZEB2 相互作用在急性淋巴细胞淋巴瘤 (ALL) 中调节 LEF1 表达的分子机制。CASP8AP2、ZEB2和CtBP2之间存在相互作用,然后在下调CASP8AP2的表达后观察到CtBP2和ZEB2之间的相互作用。野生型(包含 ZEB2 结合位点)或突变型(包含突变型结合位点)LEF1将基因启动子序列插入pGL3-basic质粒,利用双荧光素酶报告基因检测系统观察CASP8AP2、ZEB2和CtBP2如何调控LEF1基因的转录。我们得出结论,CASP8AP2、CtBP2 和 ZEB2 都可以与LEF1基因启动子区域结合并降低LEF1启动子的荧光素酶活性。同时,在下调 CASP8AP2 后,ZEB2 与LEF1启动子的相互作用明显减弱。在 697 细胞系中敲除 CASP8AP2 导致干性相关基因CD44JAG1SALL4的 mRNA 表达水平显着上调. 总之,CASP8AP2 对 CtBP2 和 ZEB2 之间的相互作用至关重要,抑制 LEF1 和干性相关基因表达 ALL。

本文的补充数据可在 https://doi.org/10.1080/08880018.2022.2033369 在线获取。

更新日期:2022-02-10
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