Promoter Methylation Leads to Hepatocyte Nuclear Factor 4A Loss and Pancreatic Cancer Aggressiveness.

ABSTRACT:

Background and aims

Decoding pancreatic ductal adenocarcinoma heterogeneity and the consequent therapeutic selection remains a challenge. We aimed to characterize epigenetically regulated pathways involved in pancreatic ductal adenocarcinoma progression.

Methods

Global DNA methylation analysis in pancreatic cancer patient tissues and cell lines was performed to identify differentially methylated genes. Targeted bisulfite sequencing and in vitro methylation reporter assays were employed to investigate the direct link between site-specific methylation and transcriptional regulation. A series of in vitro loss-of-function and gain-of function studies and in vivo xenograft and the KPC (LSL-Kras ^G12D/+ ; LSL-Trp53 ^R172H/+ ; Pdx1

SUBMITTER: Hatziapostolou M 

PROVIDER: S-EPMC11330932 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature