Breaking epigenetic shackles: targeting ARID1A methylation and the PI3K/AKT/mTOR-PD-L1 axis to overcome immune escape in gastric cancer.

ABSTRACT:

Objective

AT-rich interaction domain 1A (ARID1A), is frequently mutated in cancer, leading to loss-of-function and posing challenges to therapeutic targeting. This study aimed to systematically explore epigenetic regulation of ARID1A, specifically promoter hypermethylation, in gastric cancer (GC) and its functional/immunological consequences.

Methods

We employed multi-omics bioinformatics analyses (UALCAN, cBioPortal, MEXPRESS and UCSC Xena) combined with in vitro functional validation in GC cell lines, including pharmacological demethylation using 5-Aza-2'-deoxycytidine (5-aza-CdR) and mechanistic interrogation via AKT agonism (SC79).

Results

Promoter hypermethylation was identified as a key mechanism silencing ARID1A transcriptional, showing a signific

SUBMITTER: Duan X 

PROVIDER: S-EPMC12596888 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature