Project description:Persistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. We examined the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and found that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene was increased in Hp-positive human gastric biopsies as compared to Hp-negative controls. Moreover silencing of miR-210 in gastric epithelial cells promoted proliferation. We identified STMN1 and DIMT1 as miR-210 target genes and demonstrated that inhibition of miR-210 expression augmented cell proliferation by activating STMN1 and DIMT1. Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection. To identify miR-210 targets in gastric cells, whole transcriptome analysis of AGS and MKN45 cells transfected with pre-miR-210 was conducted using Affymetrix GeneChip Human Genome U133 Plus 2.0 Array.
Project description:Persistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. We examined the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and found that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene was increased in Hp-positive human gastric biopsies as compared to Hp-negative controls. Moreover silencing of miR-210 in gastric epithelial cells promoted proliferation. We identified STMN1 and DIMT1 as miR-210 target genes and demonstrated that inhibition of miR-210 expression augmented cell proliferation by activating STMN1 and DIMT1. Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection.
Project description:Helicobacter pylori (H. pylori) is a human pathogen that infects almost half of the world’s population. Infection with H. pylori is frequently associated with chronic gastritis and can even lead to gastric and duodenal ulcers and gastric cancer. Although the persistent colonization of H. pylori and the development of H. pylori-associated gastritis remain poorly understood, it is believed that, in gastric mucosa, the modulated gastric epithelial cells (GECs) by H. pylori are key contributors. We used microarrays to detail the global programme of gene expression in Helicobacter pylori infected-gastric epithelial cell line AGS cells and identified up-regulated genes induced by Helicobacter pylori infection.
Project description:To study the miRNA expression profiles and explore the underlying roles of Helicobacter pylori (H. pylori), miR-196a/b-5p, and IFG2BP1 in the carcinogenesis of gastric mucosa.
Project description:Helicobacter pylori clinical isolates can establish themselves in gastric epithelial stem cells and this interaction may have implications for gastric tumorigenesis. Mouse gastric epithelial progenitor cells (mGEPs) and non-progenitor gastric epithelial cells (npGECs) were infected for 24hrs with Helicobacter pylori clinical isolates Kx1 and Kx2. Kx1 was isolated from a patient with chronic atrophic gastritis (ChAG) and Kx2 from the same patient 4 years later, when he progressed to gastric adenocarcinoma. Keywords: RNA Expression Array
Project description:Helicobacter pylori clinical isolates can establish themselves in gastric epithelial stem cells and this interaction may have implications for gastric tumorigenesis. Mouse gastric epithelial progenitor cells (mGEPs) were infected for 24hrs with Helicobacter pylori clinical isolates Kx1 and Kx2. Kx1 and Kx2 were also grown in cell media in the absence of cells. Kx1 was isolated from a patient with chronic atrophic gastritis (ChAG) and Kx2 from the same patient 4 years later, when he progressed to gastric adenocarcinoma. Keywords: RNA Expression Array
Project description:Helicobacter pylori infection reprograms host gene expression and influences various cellular processes, which have been investigated by cDNA microarray in vitro culture cells and in vivo patients of the chronic abdominal complaint. In this study,the effects of H. pylori infection on host gene expression in the gastric antral mucosa of patients with chronic gastritis were examined. The gastric antral mucosa was obtained from a total of 6 untreated patients undergoing gastroscopic and pathologic confirmation of chronic superficial gastritis. Three patients infected by H. pylori and 3 patients uninfected were used to cDNA microarray experiment.
Project description:Helicobacter pylori infection reprograms host gene expression and influences various cellular processes, which have been investigated by cDNA microarray in vitro culture cells and in vivo patients of the chronic abdominal complaint. In this study,the effects of H. pylori infection on host gene expression in the gastric antral mucosa of patients with chronic gastritis were examined.
Project description:Helicobacter pylori clinical isolates can establish themselves in gastric epithelial stem cells and this interaction may have implications for gastric tumorigenesis. Mouse gastric epithelial progenitor cells (mGEPs) and non-progenitor gastric epithelial cells (npGECs) were infected for 24hrs with Helicobacter pylori clinical isolates Kx1 and Kx2. Kx1 was isolated from a patient with chronic atrophic gastritis (ChAG) and Kx2 from the same patient 4 years later, when he progressed to gastric adenocarcinoma. Experiment Overall Design: mGEPs and npGECs were seeded and grown to 70% confluency in RPMI1640 medium supplemented with 10% FBS before being infected with H. pylori strains Kx1 or Kx2 that had been grown to log phase. After 24h, media and non-attached bacteria were washed off and the cells harvested by trypsinization. RNA was prepared from triplicate cultures of mGEP cells infected with Kx1 or Kx2, npGECs infected with Kx1 or Kx2 and uninfected mGEPs and npGECs that served as controls.
Project description:Helicobacter pylori (H. pylori) is a highly successful pathogen that constitutes a serious threat to human health. However, the dynamic interaction between H. pylori and human gastric epithelium has not been fully documented. Here, by leveraging the advantage of dual RNA sequencing technology, we characterized a cytotoxin-associated genes A (CagA)-modulated bacterial adoption strategy by reinforcing the expression of ATP-binding cassette (ABC) transporter-related genes, metQ and HP_0888 upon co-culturing with human gastric epithelial cells (GES-1), thus, to benefit intracellular H. pylori survival through facilitating the uptake of host-provided nutrients. We further detected a generally repressed impact on electron transportation-associated genes by CagA, leading to the activation of oxidative phosphorylation. Temporal profiling of host mRNA signatures revealed down-regulation of multiple splicing regulators elicited by bacterial infection. Consequently, aberrant pre-mRNA splicing of functional genes that were involved in cell cycle process in response to H. pylori infection were identified. Moreover, we verified a protective effect for gastric H. pylori colonization against chronic dextran sulfate sodium (DSS)-induced colitis. Mechanistically, we profiled a cluster of short chain fatty acids (SCFA)-producing bacteria, Muribaculaceae that was selectively enriched in H. pylori-pre-colonized mice colon, contributing to the restoration of intestinal barrier function damaged by DSS treatment. Taken together, this study represents the first dual-transcriptome analysis of H. pylori during dynamic interaction with gastric epithelium and provide new insights into H. pylori pathogenesis.