Integrated analysis of genes encoding ATP-dependent chromatin remodellers identifies CHD7 as a potential target for colorectal cancer therapy.
Xingyan ZhangYaoyao ZhouZhenyu ShiZhenfeng LiuHao ChenXiaochen WangYiming ChengLishan XiXuanyuan LiChunze ZhangLi BaoChenghao XuanPublished in: Clinical and translational medicine (2022)
Our data showed that many ATPCRs represented a high frequency of somatic copy number alterations, widespread somatic mutations, remarkable expression abnormalities, and significant correlation with overall survival, suggesting several somatic driver candidates including chromodomain helicase DNA-binding protein 7 (CHD7) in colorectal cancer. We experimentally demonstrated that CHD7 promotes the growth of colorectal cancer cells in vitro and in vivo. CHD7 can bind to the promoters of target genes to maintain chromatin accessibility and facilitate transcription. We found that CHD7 knockdown downregulates AK4 expression and activates AMPK phosphorylation, thereby promoting the phosphorylation and stability of p53 and leading to the inhibition of the colorectal cancer growth. Our muti-omics analyses of ATPCRs across large-scale cancer specimens identified potential therapeutic targets and our experimental studies revealed a novel CHD7-AK4-AMPK-p53 axis that plays an oncogenic role in colorectal cancer.
Keyphrases
- machine learning
- copy number
- genome wide
- high frequency
- mitochondrial dna
- big data
- binding protein
- dna methylation
- transcription factor
- cancer therapy
- poor prognosis
- protein kinase
- transcranial magnetic stimulation
- gene expression
- dna damage
- drug delivery
- electronic health record
- circulating tumor
- long non coding rna
- climate change
- oxidative stress
- data analysis