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Aldehyde oxidase 1 promoted the occurrence and development of colorectal cancer by up-regulation of expression of CD133.
International Immunopharmacology ( IF 5.6 ) Pub Date : 2020-05-26 , DOI: 10.1016/j.intimp.2020.106618
Wenlei Zhang 1 , Wei Chai 2 , Zifeng Zhu 1 , Xingliang Li 3
Affiliation  

Aldehyde oxidase 1 (AOX1) is involved in the detoxification of a variety of aldehydes and nitrogenous heterocyclic compounds. Some reports showed that downregulation of AOX1 was associated with cancers. To probe the mechanism of AOX1 in the development of colorectal cancer, AOX1 expression in clinic specimens and various colorectal cell lines were determined. The results showed that AOX1 expression was downregulated in the cancer genome atlas data, clinic samples and various colorectal cell lines. Moreover, high expression of AOX1 promoted proliferation and invasion and inhibited apoptosis via reactive oxygen species (ROS) production. The histone biomarkers in the promoter of CD133 and regulation proteins were also analyzed using Chip assay and Western blot, which showed that AOX1 promoted the transcription and translation of CD133. In AOX1−/−APCmin/+ mice, the expression levels of CD133, p-PI3K and p-Akt protein in cancer tissues was significantly decreased and the survival rates were greatly increased. In conclusion, we found that AOX1 showed significantly positive correlation with CD133 in vitro and in vivo, indicating that AOX1 could be a potential candidate target for colorectal treatment.



中文翻译:

醛氧化酶1通过上调CD133的表达促进结直肠癌的发生和发展。

醛氧化酶1(AOX1)参与多种醛和含氮杂环化合物的解毒。一些报告表明,AOX1的下调与癌症有关。为了探讨AOX1在结直肠癌发展中的作用机理,确定了AOX1在临床标本和各种结直肠细胞系中的表达。结果表明,AOX1表达在癌症基因组图谱数据,临床样本和各种结直肠细胞系中均下调。此外,AOX1的高表达通过活性氧(ROS)的产生促进增殖和侵袭并抑制细胞凋亡。还使用芯片分析和蛋白质印迹分析了CD133启动子和调节蛋白中的组蛋白生物标志物,表明AOX1促进了CD133的转录和翻译。在AOX1中-/- APC min / +小鼠癌组织中CD133,p-PI3K和p-Akt蛋白的表达水平明显降低,存活率大大提高。总之,我们发现,AOX1表现出与CD133显著的正相关关系在体外体内,表明AOX1可能是结直肠癌治疗的潜在候选目标。

更新日期:2020-05-26
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