Alternative methylation of intron motifs is associated with cancer-related gene expression in both canine mammary tumor and human breast cancer.

Clinical Epigenetics
A-Reum NamJe-Yoel Cho

Abstract

Canine mammary tumor (CMT) has long been considered as a good animal model for human breast cancer (HBC) due to their pathological and biological similarities. However, only a few aspects of the epigenome have been explored in both HBC and CMT. Moreover, DNA methylation studies have mainly been limited to the promoter regions of genes. Genome-wide methylation analysis was performed in CMT and adjacent normal tissues and focused on the intron regions as potential targets for epigenetic regulation. As expected, many tumor suppressors and oncogenes were identified. Of note, most cancer-associated biological processes were enriched in differentially methylated genes (DMGs) that included intron DMRs (differentially methylated regions). Interestingly, two PAX motifs, PAX5 (tumor suppressive) and PAX6 (oncogenic), were frequently found in hyper- and hypomethylated intron DMRs, respectively. Hypermethylation at the PAX5 motifs in the intron regions of CDH5 and LRIG1 genes were found to be anti-correlated with gene expression, while CDH2 and ADAM19 genes harboring hypomethylated PAX6 motifs in their intron region were upregulated. These results were validated from the specimens originally MBD-sequenced as well as additional clinical sam...Continue Reading

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Citations

Nov 22, 2020·International Journal of Molecular Sciences·Johannes J SchabortJe-Yoel Cho
Oct 12, 2021·Frontiers in Veterinary Science·Marcella MassiminiLeonardo Della Salda

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Datasets Mentioned

BETA
C0006142
GSE1872
GSE26910
GSE3744
GSE24514
GSE26051
GSE15041
GSE21422
PRJNA527698

Methods Mentioned

BETA
methylation profiling
MBD-seq
RNA-seq
PCR

Software Mentioned

Ensembl BioMart
edge
Bowtie2
R package
MEDIPS
CuffLinks
integrative genomic viewer ( IGV )
IGV
Ensembl
Trim Galore

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