Epigenetic and transcriptional dysregulation of VWA2 associated with a MYC-driven oncogenic program in colorectal cancer.

ABSTRACT: VWA2 encodes AMACO, a secreted protein up-regulated in most colorectal carcinomas (CRC), constituting a promising biomarker. The mechanism responsible for its aberrant up-regulation has not been previously described. In this work, we analyzed VWA2 DNA methylation in over 400 primary CRCs. No epigenetic alterations were found in its promoter-associated CpG island. However, the region located downstream of the transcriptional start site was hypomethylated in most CRCs. ChIP-Seq revealed increased levels of the active mark H3K4me3 and reduction of the repressive mark H3K27me3. In contrast, several CRC cell lines exhibited hypermethylation of VWA2. 5-AZA-2-deoxycitidine treatment led to transcriptional activation of VWA2, supporting a functional link between DNA methylation and transcription.

SUBMITTER: Gonzalez B 

PROVIDER: S-EPMC6056412 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature