IFNγ-dependent silencing of TFF1 during Helicobacter pylori infection.
D ElettoF MentucciM VllahuA VoliA PetrellaF BoccellatoT F MeyerA PortaAlessandra ToscoPublished in: Open biology (2022)
Chronic Helicobacter pylori infection is the leading cause of intestinal-type adenocarcinoma, as prolonged Helicobacter colonization triggers chronic active gastritis, which may evolve into adenocarcinoma of the intestinal type. In this environment, cytokines play a significant role in determining the evolution of the infection. In combination with other factors (genetic, environmental and nutritional), the pro-inflammatory response may trigger pro-oncogenic mechanisms that lead to the silencing of tumour-suppressor genes, such as trefoil factor 1 (TFF1). The latter is known to play a protective role by maintaining the gastric mucosa integrity and retaining H. pylori in the mucus layer, preventing the progression of infection and, consequently, the development of gastric cancer (GC). Since TFF1 expression is reduced during chronic Helicobacter infection with a loss of gastric mucosa protection, we investigated the molecular pathways involved in this reduction. Specifically, we evaluated the effect of some pro-inflammatory cytokines on TFF1 regulation in GC and primary gastric cells by RT-qPCR and luciferase reporter assay analyses and the repressor role of the transcription factor C/EBPβ, overexpressed in gastric-intestinal cancer. Our results show that, among several cytokines, IFNγ stimulates C/EBPβ expression, which acts as a negative regulator of TFF1 by binding its promoter at three different sites.
Keyphrases
- helicobacter pylori infection
- transcription factor
- helicobacter pylori
- inflammatory response
- poor prognosis
- anti inflammatory
- squamous cell carcinoma
- genome wide
- immune response
- gene expression
- dna binding
- dna methylation
- induced apoptosis
- dendritic cells
- binding protein
- crispr cas
- radiation therapy
- papillary thyroid
- young adults
- drug induced
- locally advanced
- atomic force microscopy
- toll like receptor
- oxidative stress
- endoplasmic reticulum stress
- single molecule
- cell cycle arrest
- cell proliferation
- cell death
- rectal cancer
- high speed
- high resolution