LINC00184 promotes esophageal squamous cell carcinoma progression via DNMT1-mediated methylation of the NDRG2 promoter and PI3K/AKT pathway activation.

Abstract

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer with poor clinical outcomes, highlighting the need for enhanced understanding of its molecular drivers. The present study investigated the functional role of long non-coding RNA LINC00184 in ESCC progression. Using overexpression experiments in KYSE-150 and TE-1 cell lines, the present study demonstrated that LINC00184 significantly enhances ESCC cell proliferation and migration while inhibiting apoptosis. Mechanistic studies revealed that LINC00184 recruits DNA methyltransferase 1 (DNMT1) to the promoter of the tumor suppressor gene N-Myc downstream regulated gene 2 (NDRG2), thereby catalyzing CpG island hypermethylation and transcriptional silencing of NDRG2. The subsequent downregulation of NDRG2 results in activation of the oncogenic PI3K/AKT signaling pathway. Notably, treatment with the DNMT1 inhibitor 5-azacytidine reverses LINC00184-induced NDRG2 promoter methylation, restores NDRG2 expression and attenuates PI3K/AKT pathway activation. The present study findings identified a novel LINC00184/DNMT1/NDRG2/PI3K-AKT regulatory axis in ESCC and suggested that targeting this epigenetic pathway may represent a promising therapeutic strategy in the future.