Hypomethylation-mediated upregulation of PHOX1 promotes gastric cancer progression via transactivation of NGFR.

ABSTRACT: Gastric cancer (GC) remains a leading cause of global cancer-related mortality with limited therapeutic options, and its molecular mechanisms are incompletely understood. Through integrative analysis of TCGA and GEO datasets, coupled with clinical cohort validation, we identified frequent overexpression of the transcription factor PHOX1 in GC tissues, which correlated significantly with advanced T/M stages and poor patient survival. We demonstrated that PHOX1 promoter hypomethylation, particularly at the CpG site cg04123776, drives its overexpression in GC. Functional assays revealed that overexpression of PHOX1 enhanced GC cell proliferation, migration, and invasion in vitro, while knockdown of PHOX1 inhibited these malignant behaviors. Additionally, orthotopic xenograft models confirmed

SUBMITTER: Li Y 

PROVIDER: S-EPMC12663246 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature