Marzhoseyni Zeynab, Neamati Foroogh, Khaledi Mansoor, Haddadi Mohammad Hossein, Sadeghi Aydin, Yekani Mina, Memar Mohammad Yousef
Department of Paramedicine, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran.
Infectious Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran.
Inflammopharmacology. 2025 Sep 17. doi: 10.1007/s10787-025-01957-x.
Gastric cancer (GC) remains a significant global health burden with Helicobacter pylori (H. pylori) infection considered a primary risk factor. However, the precise molecular mechanisms of this relationship are still being elucidated. Recent studies have revealed that long non-coding RNAs (lncRNAs) play a crucial role in regulating gene expression, significantly impacting various biological processes, including carcinogenesis. LncRNAs are non-protein-coding transcripts that are over 200 nucleotides long. It has been reported that lncRNAs play a dual role, in promoting or inhibiting cancer progression through intricate molecular pathways in H. pylori-associated GC. The aim of this study was to provide an overview of the role of lncRNAs in the pathogenesis of GC induced by H. pylori. Upregulated lncRNAs such as H19, GClnc1, LINC00152, and PVT1 in H. pylori-infected patients contribute to tumorigenesis by enhancing cell proliferation, migration, invasion, and inflammation. This is often achieved through interactions with oncogenic pathways, stabilization of pro-tumor proteins, or acting as sponges for tumor-suppressive microRNAs. The mechanisms of lncRNA action are diverse, encompassing epigenetic, transcriptional, and post-transcriptional regulation, as well as influencing protein interactions and key signaling pathways, such as Wnt/β-catenin, PI3K/AKT, and NF-κB. Furthermore, lncRNAs are implicated in DNA damage and genomic instability induced by H. pylori, as well as in creating the tumor microenvironment by regulating angiogenesis and immune evasion. This multifaceted involvement positions lncRNAs as promising diagnostic, prognostic, and therapeutic markers for H. pylori-associated GC, warranting further investigation for novel clinical interventions.
胃癌（GC）仍然是一个重大的全球健康负担，幽门螺杆菌（H. pylori）感染被认为是主要风险因素。然而，这种关系的确切分子机制仍在阐明之中。最近的研究表明，长链非编码RNA（lncRNAs）在调节基因表达中起关键作用，对包括致癌作用在内的各种生物学过程有重大影响。lncRNAs是长度超过200个核苷酸的非蛋白质编码转录本。据报道，lncRNAs在幽门螺杆菌相关胃癌中通过复杂的分子途径发挥双重作用，促进或抑制癌症进展。本研究的目的是概述lncRNAs在幽门螺杆菌诱导的胃癌发病机制中的作用。幽门螺杆菌感染患者中上调的lncRNAs，如H19、GClnc1、LINC00152和PVT1，通过增强细胞增殖、迁移、侵袭和炎症促进肿瘤发生。这通常是通过与致癌途径相互作用、稳定促肿瘤蛋白或充当肿瘤抑制性微小RNA的海绵来实现的。lncRNA的作用机制多种多样，包括表观遗传、转录和转录后调控，以及影响蛋白质相互作用和关键信号通路，如Wnt/β-连环蛋白、PI3K/AKT和NF-κB。此外，lncRNAs与幽门螺杆菌诱导的DNA损伤和基因组不稳定有关，也与通过调节血管生成和免疫逃逸创造肿瘤微环境有关。这种多方面的参与使lncRNAs成为幽门螺杆菌相关胃癌有前景的诊断、预后和治疗标志物，值得进一步研究以开发新的临床干预措施。
