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

IF 6 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2025-10-03 DOI:10.1186/s12935-025-03954-0

Xing Liu, Yichun Zhao, Yueyue Zhou, Xihuan Zou, Ruobing Chen, Yuting Peng, Meng Yu

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引用次数: 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.

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n -亚硝基化合物和lncRNA NEAT1在胃上皮细胞内质网应激和恶性转化中的调节作用。

本研究以n -甲基-n′-硝基-n -亚硝基胍（MNNG）为模型致癌物，研究长期暴露于n -亚硝基化合物（NOCs）后胃上皮细胞（GES-1）和腺癌细胞（AGS）的早期致癌转化。长时间的MNNG处理增强了增殖、迁移、侵袭和不依赖锚定的生长。这些影响伴随着内质网应激（ERS）和自噬的持续激活，其特征是PERK、eIF2α、ATF4、CHOP、Beclin-1和LC3-II升高，p62降低。长链非编码RNA核富集丰富转录本1 （NEAT1）显著上调，并作为竞争内源RNA，海绵microRNA-329-3p （miR-329-3p）抑制ATF4。沉默NEAT1或恢复miR-329-3p表达可抑制ERS、自噬和恶性性状。这些发现建立了NEAT1/miR-329-3p/ATF4信号轴，将应激反应与早期胃上皮转化联系起来，为干预提供了潜在的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.