Regulatory role of N-nitroso compounds and lncRNA NEAT1 in endoplasmic reticulum stress and malignant transformation of gastric epithelial cells

• Published in: Cancer Cell International
• Main Authors: Xing Liu, Yichun Zhao, Yueyue Zhou, Xihuan Zou, Ruobing Chen, Yuting Peng, Meng Yu
• Format: Article
• Language: English
• Published: BMC 2025-10-01
• Subjects: N-nitroso compounds; Endoplasmic reticulum stress; NEAT1; MiR-329-3p; Gastric cancer
• Online Access: https://doi.org/10.1186/s12935-025-03954-0

Abstract This study investigates the early oncogenic transformation of gastric epithelial cells (GES-1) and adenocarcinoma cells (AGS) following long-term exposure to N-nitroso compounds (NOCs), using N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) as a model carcinogen. Prolonged MNNG treatment enhanced proliferation, migration, invasion, and anchorage-independent growth. These effects were accompanied by persistent activation of endoplasmic reticulum stress (ERS) and autophagy, characterized by elevated PERK, eIF2α, ATF4, CHOP, Beclin-1, and LC3-II, and reduced p62. Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) was markedly upregulated and acted as a competing endogenous RNA, sponging microRNA-329-3p (miR-329-3p) to derepress ATF4. Silencing NEAT1 or restoring miR-329-3p expression suppressed ERS, autophagy, and malignant traits. These findings establish a NEAT1/miR-329-3p/ATF4 signaling axis that links stress response to early gastric epithelial transformation, offering a potential target for intervention.