Evidence map›Paper›PMID 39915880›Full record

ArticleBMC medicine2025

Helicobacter pylori SlyD stabilizes TPT1 via hnRNPK and enhances OCT1-mediated CDX2 transcriptional activation to drive gastric intestinal metaplasia.

Shuwen Zheng, Yingying Wang, Chuxuan Ni, Rui Guo, Xunan Qiu, Jijun Chen, Lu Wang, Xiaohu Sun, Moye Chen, Yunen Liu and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Shuwen ZhengTumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, 110001, China.
Yingying WangTumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, 110001, China.
Chuxuan NiTumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, 110001, China.
Rui GuoTumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, 110001, China.
Xunan QiuTumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, 110001, China.
Jijun ChenTumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, 110001, China.
Lu WangTumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, 110001, China.
Xiaohu SunTumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, 110001, China.
Moye ChenTumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, 110001, China.
Yunen LiuTumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, 110001, China.
Yuan YuanTumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, 110001, China. yuanyuan@cmu.edu.cn.
Yuehua GongTumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, 110001, China. yhgong@cmu.edu.cn.

Funding

the National Natural Science Foundation of China No.81970501the Science and Technology Plan of Shenyang No.: 22-321-32-03
6 · The paper itself

Abstract

backgroundGastric intestinal metaplasia (GIM) represents an important precancerous lesion in intestinal-type gastric cancer, triggered by persistent Helicobacter pylori (H. pylori) infection. In a previous study, we unveiled SlyD as a novel virulence factor of H. pylori, establishing its role in GIM induction through TPT1. However, the underlying mechanism remains undetermined.

methodsGastric epithelial cells were stimulated with H. pylori 26695, a SlyD inactivated mutant (ΔSlyD), and purified HpSlyD protein, respectively. Real-time qPCR and western blot were subsequently used to assess the expression levels of hnRNPK, TPT1, OCT1, and GIM markers. RNA sequencing was employed to identify differentially expressed genes associated with H. pylori SlyD infection. Protein stability was evaluated using cycloheximide. Molecular interactions were investigated through co-immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. Additionally, molecular docking was utilized to predict TPT1 inhibitors. Immunohistochemistry staining was conducted to validate hnRNPK, TPT1, OCT1, and CDX2 expression in gastric tissue samples from both human and Mongolian gerbils.

resultsH. pylori SlyD upregulates TPT1 and induces the expression of GIM markers through hnRNPK. The interaction between hnRNPK and TPT1 enhances TPT1 protein stability, with H. pylori SlyD intensifying this association. TPT1 promotes the expression of GIM markers mediated via OCT1, which binds to CDX2 promoter region, thereby modulating its transcriptional activity. Dihydroartemisinin has the potential to target TPT1, inhibiting the H. pylori SlyD-induced expression of GIM markers.

conclusionsIn vitro and in vivo experiments verified that H. pylori SlyD enhances TPT1 stability through hnRNPK, leading to OCT1-mediated transcriptional activation of CDX2 and the initiation of the GIM process. Our study offers novel perspectives on the pathogenesis of H. pylori-related gastric precancerous conditions.

Indexed as

Bacterial ProteinsCDX2 Transcription FactorHelicobacter InfectionsHelicobacter pyloriHeterogeneous-Nuclear Ribonucleoprotein KAnimalsGastric MucosaGerbillinaeHumansMetaplasiaStomach NeoplasmsTranscriptional ActivationTumor Protein, Translationally-Controlled 1Bacterial ProteinsCDX2 protein, humanCDX2 Transcription FactorHeterogeneous-Nuclear Ribonucleoprotein KHNRNPK protein, humanTPT1 protein, humanTumor Protein, Translationally-Controlled 1CDX2DihydroartemisininGastric intestinal metaplasiaGastric precancerous diseaseH. pyloriSlyD

Identifiers

PMID39915880
PMCPMC11803974

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.