Signaling pathways of oxidative stress response: the potential therapeutic targets in gastric cancer

Liu, Yingying; Shi, Yu; Han, Ruiqin; Liu, Chaoge; Qin, X.; Li, Pengfei; Gu, Renjun

doi:10.3389/fimmu.2023.1139589

Cited by 24 publications

(9 citation statements)

References 164 publications

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“…Moreover, we observed an inhibitory impact of H. pylori cagA on electron transportation, as evidenced by the general repression of a set of ETC-related genes. The disrupted oxidative phosphorylation process could lead to the accumulation of ROS in host cells, thereby causing DNA damage and chromosomal instability and thus offering a pathological potential for gastric carcinogenesis ( 36 ). These results enhance our understanding of the pathogenic mechanisms of cagA -positive H. pylori strains upon colonization in the human stomach.…”

Section: Discussionmentioning

confidence: 99%

Dual RNA sequencing of Helicobacter pylori and host cell transcriptomes reveals ontologically distinct host-pathogen interaction

Hu,

Zhai,

Huang

et al. 2024

mSystems

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Helicobacter pylori is a highly successful pathogen that poses a substantial threat to human health. However, the dynamic interaction between H. pylori and the human gastric epithelium has not been fully investigated. In this study, using dual RNA sequencing technology, we characterized a cytotoxin-associated gene A ( cagA )-modulated bacterial adaption strategy by enhancing the expression of ATP-binding cassette transporter-related genes, metQ and HP_0888 , upon coculturing with human gastric epithelial cells. We observed a general repression of electron transport-associated genes by cagA , leading to the activation of oxidative phosphorylation. Temporal profiling of host mRNA signatures revealed the downregulation of multiple splicing regulators due to bacterial infection, resulting in aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. Moreover, we demonstrated a protective effect of gastric H. pylori colonization against chronic dextran sulfate sodium (DSS)-induced colitis. Mechanistically, we identified a cluster of propionic and butyric acid-producing bacteria, Muribaculaceae , selectively enriched in the colons of H. pylori -pre-colonized mice, which may contribute to the restoration of intestinal barrier function damaged by DSS treatment. Collectively, this study presents the first dual-transcriptome analysis of H. pylori during its dynamic interaction with gastric epithelial cells and provides new insights into strategies through which H. pylori promotes infection and pathogenesis in the human gastric epithelium. IMPORTANCE Simultaneous profiling of the dynamic interaction between Helicobacter pylori and the human gastric epithelium represents a novel strategy for identifying regulatory responses that drive pathogenesis. This study presents the first dual-transcriptome analysis of H. pylori when cocultured with gastric epithelial cells, revealing a bacterial adaptation strategy and a general repression of electron transportation-associated genes, both of which were modulated by cytotoxin-associated gene A ( cagA ). Temporal profiling of host mRNA signatures dissected the aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. We demonstrated a protective effect of gastric H. pylori colonization against chronic DSS-induced colitis through both in vitro and in vivo experiments. These findings significantly enhance our understanding of how H. pylori promotes infection and pathogenesis in the human gastric epithelium and provide evidence to identify targets for antimicrobial therapies.

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Section: Discussionmentioning

confidence: 99%

Dual RNA sequencing of Helicobacter pylori and host cell transcriptomes reveals ontologically distinct host-pathogen interaction

Hu,

Zhai,

Huang

et al. 2024

mSystems

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“…The COVID-19 dataset showed enrichment in the PLK1 pathway, associated with stem cell cancer ( 50 ), glioma ( 51 ), and lung adenocarcinoma ( 52 ). The influenza dataset exhibited enrichment in the oxidative stress response signaling pathway, a potential therapeutic target for gastric cancer ( 53 ). Furthermore, the HIV dataset showed enrichment in the mitochondrial translation pathway, which is crucial for the continuous cytotoxicity of T lymphocytes (CTL) ( 54 ).…”

Section: Discussionmentioning

confidence: 99%

“…The interconnected regulatory interaction network of Hub genes-miRNAs and Hub genes-TFs. pathway, a potential therapeutic target for gastric cancer (53). Furthermore, the HIV dataset showed enrichment in the mitochondrial translation pathway, which is crucial for the continuous cytotoxicity of T lymphocytes (CTL) (54).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics and system biology approach to identify the influences among COVID-19, influenza, and HIV on the regulation of gene expression

Zhang,

Jin,

Zhang

et al. 2024

Front. Immunol.

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BackgroundCoronavirus disease (COVID-19), caused by SARS-CoV-2, has emerged as a infectious disease, coexisting with widespread seasonal and sporadic influenza epidemics globally. Individuals living with HIV, characterized by compromised immune systems, face an elevated risk of severe outcomes and increased mortality when affected by COVID-19. Despite this connection, the molecular intricacies linking COVID-19, influenza, and HIV remain unclear. Our research endeavors to elucidate the shared pathways and molecular markers in individuals with HIV concurrently infected with COVID-19 and influenza. Furthermore, we aim to identify potential medications that may prove beneficial in managing these three interconnected illnesses.MethodsSequencing data for COVID-19 (GSE157103), influenza (GSE185576), and HIV (GSE195434) were retrieved from the GEO database. Commonly expressed differentially expressed genes (DEGs) were identified across the three datasets, followed by immune infiltration analysis and diagnostic ROC analysis on the DEGs. Functional enrichment analysis was performed using GO/KEGG and Gene Set Enrichment Analysis (GSEA). Hub genes were screened through a Protein-Protein Interaction networks (PPIs) analysis among DEGs. Analysis of miRNAs, transcription factors, drug chemicals, diseases, and RNA-binding proteins was conducted based on the identified hub genes. Finally, quantitative PCR (qPCR) expression verification was undertaken for selected hub genes.ResultsThe analysis of the three datasets revealed a total of 22 shared DEGs, with the majority exhibiting an area under the curve value exceeding 0.7. Functional enrichment analysis with GO/KEGG and GSEA primarily highlighted signaling pathways associated with ribosomes and tumors. The ten identified hub genes included IFI44L, IFI44, RSAD2, ISG15, IFIT3, OAS1, EIF2AK2, IFI27, OASL, and EPSTI1. Additionally, five crucial miRNAs (hsa-miR-8060, hsa-miR-6890-5p, hsa-miR-5003-3p, hsa-miR-6893-3p, and hsa-miR-6069), five essential transcription factors (CREB1, CEBPB, EGR1, EP300, and IRF1), and the top ten significant drug chemicals (estradiol, progesterone, tretinoin, calcitriol, fluorouracil, methotrexate, lipopolysaccharide, valproic acid, silicon dioxide, cyclosporine) were identified.ConclusionThis research provides valuable insights into shared molecular targets, signaling pathways, drug chemicals, and potential biomarkers for individuals facing the complex intersection of COVID-19, influenza, and HIV. These findings hold promise for enhancing the precision of diagnosis and treatment for individuals with HIV co-infected with COVID-19 and influenza.

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“…Gastrointestinal-related cancers exhibit an increased production of ROS than in the case of body homeostasis. High levels of ROS cause DNA damage, inactivate tumor suppressor genes, and act as signaling molecules, interacting directly with receptors to disrupt signaling pathways [ 35 , 57 , 58 ]. ROS also leads to chronic inflammation by activating COX-2 secretion, pro-inflammatory interleukins, and even TNFα [ 35 , 41 , 59 ].…”

Section: Properties and Molecular Mechanisms Of Betulin And Its Deriv...mentioning

confidence: 99%

Synthesis, Pharmacological Properties, and Potential Molecular Mechanisms of Antitumor Activity of Betulin and Its Derivatives in Gastrointestinal Cancers

Madej,

Gola,

Chrobak

2023

Pharmaceutics

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Gastrointestinal (GI) cancers are an increasingly common type of malignancy, caused by the unhealthy lifestyles of people worldwide. Limited methods of treatment have prompted the search for new compounds with antitumor activity, in which betulin (BE) is leading the way. BE as a compound is classified as a pentacyclic triterpene of the lupane type, having three highly reactive moieties in its structure. Its mechanism of action is based on the inhibition of key components of signaling pathways associated with proliferation, migration, interleukins, and others. BE also has a number of biological properties, i.e., anti-inflammatory, hepatoprotective, neuroprotective, as well as antitumor. Due to its poor bioavailability, betulin is subjected to chemical modifications, obtaining derivatives with proven enhanced pharmacological and pharmacokinetic properties as a result. The method of synthesis and substituents significantly influence the effect on cells and GI cancers. Moreover, the cytotoxic effect is highly dependent on the derivative as well as the individual cell line. The aim of this study is to review the methods of synthesis of BE and its derivatives, as well as its pharmacological properties and molecular mechanisms of action in colorectal cancer, hepatocellular carcinoma, gastric cancer, and esophageal cancer neoplasms.

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Signaling pathways of oxidative stress response: the potential therapeutic targets in gastric cancer

Cited by 24 publications

References 164 publications

Dual RNA sequencing of Helicobacter pylori and host cell transcriptomes reveals ontologically distinct host-pathogen interaction

Dual RNA sequencing of Helicobacter pylori and host cell transcriptomes reveals ontologically distinct host-pathogen interaction

Bioinformatics and system biology approach to identify the influences among COVID-19, influenza, and HIV on the regulation of gene expression

Synthesis, Pharmacological Properties, and Potential Molecular Mechanisms of Antitumor Activity of Betulin and Its Derivatives in Gastrointestinal Cancers

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