幽门螺杆菌感染上调 LncRNA-LINC00659 的表达，通过调节 PTBP1 的表达促进胃炎向癌症的进展。

Upregulated LncRNA-LINC00659 expression by H. pylori infection promoted the progression of gastritis to cancer by regulating PTBP1 expression.

机构信息

School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R. China.

Department of Gastroenterology, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, Jiangsu, P. R. China.

出版信息

Indian J Pathol Microbiol. 2024 Jul 1;67(3):510-517. doi: 10.4103/ijpm.ijpm_48_23. Epub 2023 Nov 9.

DOI:10.4103/ijpm.ijpm_48_23

PMID:38394397

Abstract

CONTEXT

Helicobacter pylori ( H. pylori ), a spiral-shaped bacterium, is closely associated with chronic, progressive gastric mucosal damage, gastric atrophy, and even gastric cancer (GC). An increasing number of studies have addressed the correlation between long noncoding RNAs (lncRNAs) and H. pylori pathogenicity in GC.

OBJECTIVE

In this study, we found that the expression level of LINC00659 gradually increased in the progression from atrophic gastritis, intestinal metaplasia, and dysplasia to GC in H. pylori -infected patients. Thus, we aimed to further explore the function of LINC00659 in the progression of gastritis to cancer under H. pylori infection.

MATERIALS AND METHODS

StarBase predictions, ribonucleic acid (RNA)-binding protein immunoprecipitation assays, and gene ontology functional annotation (GO)/Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to identify the RNA-binding proteins of LINC00659; moreover, qRT‒PCR, western blotting, RNA interference, and immunofluorescence assays were used to investigate the function of LINC00659.

RESULTS

LINC00659 bound directly to the RNA-binding protein polypyrimidine tract-binding protein (PTBP1). Importantly, qRT‒PCR and western blot assays demonstrated that PTBP1 expression increased in the progression from inflammation to cancer in the stomach of H. pylori -infected patients and H. pylori -infected GES-1 cells. However, LINC00659 knockdown downregulated PTBP1 expression and inhibited PTBP1 binding under H. pylori infection. Finally, LINC00659 knockdown significantly reduced H. pylori -induced human gastric epithelial cell senescence and suppressed interleukin (IL)-6 and IL-8 secretion by reducing the phosphorylation level of NF-κB p65.

CONCLUSIONS

This study indicated that LINC00659 may have the potential to be a novel promising prognostic and therapeutic marker for H. pylori -associated gastric diseases.

摘要

背景

幽门螺杆菌（H. pylori）是一种螺旋形细菌，与慢性、进行性胃黏膜损伤、胃萎缩甚至胃癌（GC）密切相关。越来越多的研究探讨了长链非编码 RNA（lncRNAs）与 H. pylori 在 GC 发病机制中的相关性。

目的

本研究发现，在 H. pylori 感染患者从萎缩性胃炎、肠上皮化生和异型增生到 GC 的进展过程中，LINC00659 的表达水平逐渐升高。因此，我们旨在进一步探讨 LINC00659 在 H. pylori 感染下胃炎向癌症进展中的功能。

材料和方法

StarBase 预测、核糖核酸（RNA）-结合蛋白免疫沉淀测定和基因本体功能注释（GO）/京都基因与基因组百科全书（KEGG）通路分析用于鉴定 LINC00659 的 RNA 结合蛋白；此外，qRT-PCR、western blot、RNA 干扰和免疫荧光测定用于研究 LINC00659 的功能。

结果

LINC00659 直接与 RNA 结合蛋白多嘧啶 tract 结合蛋白（PTBP1）结合。重要的是，qRT-PCR 和 western blot 检测表明，在 H. pylori 感染患者和 H. pylori 感染的 GES-1 细胞中，从炎症到癌症的胃进展过程中，PTBP1 的表达增加。然而，LINC00659 敲低下调了 H. pylori 感染下的 PTBP1 表达并抑制了 PTBP1 的结合。最后，LINC00659 敲低通过降低 NF-κB p65 的磷酸化水平，显著减少了 H. pylori 诱导的人胃上皮细胞衰老，并抑制了白细胞介素（IL）-6 和 IL-8 的分泌。