ArticleCell death & disease2021
The novel ZEB1-upregulated protein PRTG induced by Helicobacter pylori infection promotes gastric carcinogenesis through the cGMP/PKG signaling pathway.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Advances inOncology letters · 2026Review
- Downregulated of CTGF reveals mechanism, remodels immune microenvironment, modulates drug sensitivity in bladder cancer.Future science OA · 2025Article
- A study on the microbiome within oropharyngeal cancer tissues.Discover oncology · 2025Article
- Potential biomarkers in early detection of gastric cancer.Frontiers in pharmacology · 2025Review
- The histone acetylation-related gene signature predicts prognosis and immunotherapy response in stomach adenocarcinoma.Frontiers in oncology · 2025Article
- Implication of protein post translational modifications in gastric cancer.Frontiers in cell and developmental biology · 2025Review
- Protogenin facilitates trunk-to-tail HOX code transition via modulating GDF11/SMAD2 signaling in mammalian embryos.Communications biology · 2024Article
- Machine learning based intratumor heterogeneity signature for predicting prognosis and immunotherapy benefit in stomach adenocarcinoma.Scientific reports · 2024Article
- The implication of integrative multiple RNA modification-based subtypes in gastric cancer immunotherapy and prognosis.iScience · 2024Article
- EDNRB inhibits the growth and migration of prostate cancer cells by activating the cGMP-PKG pathway.Open medicine (Warsaw, Poland) · 2024Article
- Investigating the prognostic and predictive value of the type II cystatin genes in gastric cancer.BMC cancer · 2023Article
- FLED: a full-length eccDNA detector for long-reads sequencing data.Briefings in bioinformatics · 2023Article
- IncreasedCancers · 2023Article
- MiR-200/183 family-mediated module biomarker for gastric cancer progression: an AI-assisted bioinformatics method with experimental functional survey.Journal of translational medicine · 2023Article
- Integrative competing endogenous RNA network analyses identify novel lncRNA and genes implicated in metastatic breast cancer.Scientific reports · 2023Article
- Article
- Comprehensive Analysis of the Transcriptome-wide m6A Methylome in Lung Adenocarcinoma by MeRIP Sequencing.Frontiers in oncology · 2022Article
- NEK7 promotes gastric cancer progression as a cell proliferation regulator.Cancer cell international · 2021Article
- High-Risk HPV16 E6 Activates the cGMP/PKG Pathway Through Glycosyltransferase ST6GAL1 in Cervical Cancer Cells.Frontiers in oncology · 2021Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Helicobacter pylori (H. pylori) is listed as a class I carcinogen in human gastric cancer; however, the underlying mechanisms are poorly understood. In this study, we identified Protogenin (PRTG) was upregulated in both gastric cancer tissues and H. pylori-infected tissues by analyzing dysregulated genes in TCGA and GEO databases. Importantly, upregulated PRTG predicted poor prognosis of gastric cancer patients and integrative analysis revealed that PRTG served as an oncogenic protein in gastric cancer and was required for H. pylori-mediated tumorigenic activities in in vitro cellular and in vivo tumor-bearing mouse models. Mechanistically, H. pylori infection enhanced PRTG expression by promoting transcriptional factor ZEB1 stabilization and recruitment to the PRTG promoter, and which then activated the sub-following cGMP/PKG signaling pathway in bioinformatic and cellular studies. Cellular studies further confirmed that PRTG depended on activating cGMP/PKG axis to promote proliferation, metastasis, and chemoresistance of gastric cancer cells. The PKG inhibitor KT5823 played synergistic anti-tumor effects with cisplatin and paclitaxel to gastric cancer cells in in vitro cellular and in vivo tumor-bearing mouse models. Taken together, our findings suggested that H. pylori infection depends on ZEB1 to induce PRTG upregulation, and which leading to the development and progression of gastric cancer through activating cGMP/PKG signaling pathway. Blocking PRTG/cGMP/PKG axis, therefore, presents a promising novel therapeutic strategy for gastric cancer.
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