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TLR2 and TLR4 Signaling Pathways and Gastric Cancer: Insights from Transcriptomics and Sample Validation

BACKGROUND: Pattern recognition receptors, especially TLRs, as the first line of defense for pathogen detection, were found to be associated with H. pylori infection and GC. However, the expression levels of TLRs, i.e. TLR2 and TLR4, as the main receptors sensed by H. pylori, still remain largely am...

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Autores principales: Zargari, Saeed, Bahari, Abbas, Goodarzi, Mohammad Taghi, Mahmoodi, Minoo, Valadan, Reza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pasteur Institute of Iran 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784901/
https://www.ncbi.nlm.nih.gov/pubmed/34773930
http://dx.doi.org/10.52547/ibj.26.1.36
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author Zargari, Saeed
Bahari, Abbas
Goodarzi, Mohammad Taghi
Mahmoodi, Minoo
Valadan, Reza
author_facet Zargari, Saeed
Bahari, Abbas
Goodarzi, Mohammad Taghi
Mahmoodi, Minoo
Valadan, Reza
author_sort Zargari, Saeed
collection PubMed
description BACKGROUND: Pattern recognition receptors, especially TLRs, as the first line of defense for pathogen detection, were found to be associated with H. pylori infection and GC. However, the expression levels of TLRs, i.e. TLR2 and TLR4, as the main receptors sensed by H. pylori, still remain largely ambiguous. We aimed to investigate the patterns of key transcripts of TLR2 and TLR4 in 100 GC transcriptome data. Additionally, we evaluated TLR2 and TLR4 gene expressions in gastric biopsies of Iranian GC patients, in order to validate RNA-seq outputs. METHODS: For this study, 100 runs of GC samples and controls were processed and analyzed using map read to reference. DGE method was used to distinguish between GC and normal samples in the expression of TLRs and other innate immune molecules. Also, using qRT-PCR assay, transcripts of TLRs molecules for 15 GC and 15 control samples were analyzed based on the analysis of variance and least significant differences. RESULTS: The results clearly showed that all signaling pathways molecules of TLR4, especially TLR4 (p = 0.019), NF-κB (p = 0.047), IL-1β (p = 0.0096), and TNF-α (p = 0.048), were upregulated in a cancerous condition in different parts and at various stages of GC. CONCLUSION: Our findings suggested that molecules involved in inflammation, including TLR4 and its related pro-inflammatory cytokines, may be responsible for the development and progression of GC. Accordingly, the control of H. pylori infection reduces inflammation in the gastric system and can play an important role in preventing gastrointestinal disorders.
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spelling pubmed-87849012022-02-07 TLR2 and TLR4 Signaling Pathways and Gastric Cancer: Insights from Transcriptomics and Sample Validation Zargari, Saeed Bahari, Abbas Goodarzi, Mohammad Taghi Mahmoodi, Minoo Valadan, Reza Iran Biomed J Full Length BACKGROUND: Pattern recognition receptors, especially TLRs, as the first line of defense for pathogen detection, were found to be associated with H. pylori infection and GC. However, the expression levels of TLRs, i.e. TLR2 and TLR4, as the main receptors sensed by H. pylori, still remain largely ambiguous. We aimed to investigate the patterns of key transcripts of TLR2 and TLR4 in 100 GC transcriptome data. Additionally, we evaluated TLR2 and TLR4 gene expressions in gastric biopsies of Iranian GC patients, in order to validate RNA-seq outputs. METHODS: For this study, 100 runs of GC samples and controls were processed and analyzed using map read to reference. DGE method was used to distinguish between GC and normal samples in the expression of TLRs and other innate immune molecules. Also, using qRT-PCR assay, transcripts of TLRs molecules for 15 GC and 15 control samples were analyzed based on the analysis of variance and least significant differences. RESULTS: The results clearly showed that all signaling pathways molecules of TLR4, especially TLR4 (p = 0.019), NF-κB (p = 0.047), IL-1β (p = 0.0096), and TNF-α (p = 0.048), were upregulated in a cancerous condition in different parts and at various stages of GC. CONCLUSION: Our findings suggested that molecules involved in inflammation, including TLR4 and its related pro-inflammatory cytokines, may be responsible for the development and progression of GC. Accordingly, the control of H. pylori infection reduces inflammation in the gastric system and can play an important role in preventing gastrointestinal disorders. Pasteur Institute of Iran 2022-01 2021-11-14 /pmc/articles/PMC8784901/ /pubmed/34773930 http://dx.doi.org/10.52547/ibj.26.1.36 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Length
Zargari, Saeed
Bahari, Abbas
Goodarzi, Mohammad Taghi
Mahmoodi, Minoo
Valadan, Reza
TLR2 and TLR4 Signaling Pathways and Gastric Cancer: Insights from Transcriptomics and Sample Validation
title TLR2 and TLR4 Signaling Pathways and Gastric Cancer: Insights from Transcriptomics and Sample Validation
title_full TLR2 and TLR4 Signaling Pathways and Gastric Cancer: Insights from Transcriptomics and Sample Validation
title_fullStr TLR2 and TLR4 Signaling Pathways and Gastric Cancer: Insights from Transcriptomics and Sample Validation
title_full_unstemmed TLR2 and TLR4 Signaling Pathways and Gastric Cancer: Insights from Transcriptomics and Sample Validation
title_short TLR2 and TLR4 Signaling Pathways and Gastric Cancer: Insights from Transcriptomics and Sample Validation
title_sort tlr2 and tlr4 signaling pathways and gastric cancer: insights from transcriptomics and sample validation
topic Full Length
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784901/
https://www.ncbi.nlm.nih.gov/pubmed/34773930
http://dx.doi.org/10.52547/ibj.26.1.36
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