Aldehyde oxidase 1 promoted the occurrence and development of colorectal cancer by up-regulation of expression of CD133.

ABSTRACT

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.