Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line

BACKGROUND: Vacuolating cytotoxin (VacA) is an important virulence factor of Helicobacter pylori (H. pylori). It was previously believed that VacA can trigger the cascade of apoptosis on mitochondria to lead to cell apoptosis. Recently, it was found that VacA can induce autophagy. However, the molec...

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Autores principales: Luo, Juan, Bai, Luyan, Tao, Jun, Wen, Yu, Li, Mingke, Zhu, Yunzhen, Luo, Sufeng, Pu, Guangyu, Ma, Lanqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429402/
https://www.ncbi.nlm.nih.gov/pubmed/34398448
http://dx.doi.org/10.1007/s13258-021-01151-7
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author Luo, Juan
Bai, Luyan
Tao, Jun
Wen, Yu
Li, Mingke
Zhu, Yunzhen
Luo, Sufeng
Pu, Guangyu
Ma, Lanqing
author_facet Luo, Juan
Bai, Luyan
Tao, Jun
Wen, Yu
Li, Mingke
Zhu, Yunzhen
Luo, Sufeng
Pu, Guangyu
Ma, Lanqing
author_sort Luo, Juan
collection PubMed
description BACKGROUND: Vacuolating cytotoxin (VacA) is an important virulence factor of Helicobacter pylori (H. pylori). It was previously believed that VacA can trigger the cascade of apoptosis on mitochondria to lead to cell apoptosis. Recently, it was found that VacA can induce autophagy. However, the molecular mechanism by which VacA induces autophagy is largely unknown. OBJECTIVE: We aimed to explore the molecular mechanism of autophagy induced by H. pylori in gastric cancer cells and the effect of autophagy on the survival of gastric cancer cells. METHODS: The autophagy of human gastric cancer cell line SGC7901 was detected by Western blot and RT-PCR in the treatment of VacA protein of H. pylori. The relationship between autophagy and reactive oxygen species (ROS) in the proliferation of gastric cancer cells were studied by gene expression silences (siRNA) and CM-H2DCFDA (DCF) staining. RESULTS: The results showed that VacA protein secreted by H. pylori in the supernatant stimulated autophagy in SGC7901 cells. After VacA protein treatment, the mRNA expressions of BECN1, ATG7 and PIK3C3, were up-regulated. ATG7 silencing by siRNA inhibited VacA-induced autophagy. Furthermore, our data demonstrated that VacA protein increased ROS levels. Addition of the antioxidant N-acetyl-l-cysteine (NAC) suppressed the levels of ROS, leading to inhibition of autophagy. CONCLUSIONS: H. pylori VacA is a key toxin that induces autophagy by increased ROS levels. And our findings demonstrated that VacA significantly inhibited proliferation in SGC7901 cells.
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spelling pubmed-84294022021-09-24 Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line Luo, Juan Bai, Luyan Tao, Jun Wen, Yu Li, Mingke Zhu, Yunzhen Luo, Sufeng Pu, Guangyu Ma, Lanqing Genes Genomics Research Article BACKGROUND: Vacuolating cytotoxin (VacA) is an important virulence factor of Helicobacter pylori (H. pylori). It was previously believed that VacA can trigger the cascade of apoptosis on mitochondria to lead to cell apoptosis. Recently, it was found that VacA can induce autophagy. However, the molecular mechanism by which VacA induces autophagy is largely unknown. OBJECTIVE: We aimed to explore the molecular mechanism of autophagy induced by H. pylori in gastric cancer cells and the effect of autophagy on the survival of gastric cancer cells. METHODS: The autophagy of human gastric cancer cell line SGC7901 was detected by Western blot and RT-PCR in the treatment of VacA protein of H. pylori. The relationship between autophagy and reactive oxygen species (ROS) in the proliferation of gastric cancer cells were studied by gene expression silences (siRNA) and CM-H2DCFDA (DCF) staining. RESULTS: The results showed that VacA protein secreted by H. pylori in the supernatant stimulated autophagy in SGC7901 cells. After VacA protein treatment, the mRNA expressions of BECN1, ATG7 and PIK3C3, were up-regulated. ATG7 silencing by siRNA inhibited VacA-induced autophagy. Furthermore, our data demonstrated that VacA protein increased ROS levels. Addition of the antioxidant N-acetyl-l-cysteine (NAC) suppressed the levels of ROS, leading to inhibition of autophagy. CONCLUSIONS: H. pylori VacA is a key toxin that induces autophagy by increased ROS levels. And our findings demonstrated that VacA significantly inhibited proliferation in SGC7901 cells. Springer Singapore 2021-08-16 2021 /pmc/articles/PMC8429402/ /pubmed/34398448 http://dx.doi.org/10.1007/s13258-021-01151-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Luo, Juan
Bai, Luyan
Tao, Jun
Wen, Yu
Li, Mingke
Zhu, Yunzhen
Luo, Sufeng
Pu, Guangyu
Ma, Lanqing
Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line
title Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line
title_full Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line
title_fullStr Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line
title_full_unstemmed Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line
title_short Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line
title_sort autophagy induced by h. pylori vaca regulated the survival mechanism of the sgc7901 human gastric cancer cell line
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429402/
https://www.ncbi.nlm.nih.gov/pubmed/34398448
http://dx.doi.org/10.1007/s13258-021-01151-7
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