<scp>DNMT1</scp> ‐Induced Downregulation of <scp>CBX7</scp> Inhibits <scp>ERK</scp> Phosphorylation and Promotes Pancreatic Ductal Adenocarcinoma Progression

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancer types, characterized by an alarmingly low 5-year survival rate. DNA methylation has been implicated in the progression of various tumors, with DNA methyltransferase 1 (DNMT1) being the most extensively studied enzyme in this context. However, the expression patterns and underlying mechanisms of DNMT1 in PDAC remain poorly understood. The levels of DNMT1 and CBX7 in PDAC tissues and cells were determined by IHC and Western blot. ChIP and dual-luciferase reporter assays confirmed the interaction between DNMT1 and the CBX7 promoter. Cellular functions were evaluated through CCK-8, wound healing, and transwell assays. The expression of MAPK-related proteins was analyzed by Western blot. DNMT1 expression was upregulated in PDAC tissues and cell lines, whereas CBX7 expression was downregulated. Silencing DNMT1 inhibited cell proliferation, migration, and invasion in PDAC by modulating CBX7 expression. Moreover, DNMT1 methylates the CBX7 promoter region, leading to increased ERK phosphorylation, which subsequently drives tumorigenesis and metastasis in PDAC. DNMT1 promotes the malignant progression of PDAC through the CBX7/ERK pathway. Our study provides evidence for potential therapeutic targets for the comprehensive treatment of PDAC.