Cargando…

LTBP2 Knockdown Promotes Ferroptosis in Gastric Cancer Cells through p62-Keap1-Nrf2 Pathway

Gastric cancer (GC) is one of the most common gastrointestinal malignancies. Ferroptosis is a new type of peroxidation-driven and iron-dependent cell death. However, the biological functions and exact regulatory mechanisms of ferroptosis in GC remain elusive. Here, we performed RNAi and gene transfe...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, TingAn, Zhou, ZiHan, Wang, ChunMiao, Qin, YuZhou, Wu, Liucheng, Hu, BangLi, Jin, QinWen, Wei, WeiYuan, Huang, MingWei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9371865/
https://www.ncbi.nlm.nih.gov/pubmed/35968244
http://dx.doi.org/10.1155/2022/6532253
_version_ 1784767254347382784
author Wang, TingAn
Zhou, ZiHan
Wang, ChunMiao
Qin, YuZhou
Wu, Liucheng
Hu, BangLi
Jin, QinWen
Wei, WeiYuan
Huang, MingWei
author_facet Wang, TingAn
Zhou, ZiHan
Wang, ChunMiao
Qin, YuZhou
Wu, Liucheng
Hu, BangLi
Jin, QinWen
Wei, WeiYuan
Huang, MingWei
author_sort Wang, TingAn
collection PubMed
description Gastric cancer (GC) is one of the most common gastrointestinal malignancies. Ferroptosis is a new type of peroxidation-driven and iron-dependent cell death. However, the biological functions and exact regulatory mechanisms of ferroptosis in GC remain elusive. Here, we performed RNAi and gene transfection, cell viability assay, lipid peroxidation assay, reactive oxygen species (ROS) assay, glutathione assay, qRT-PCR, Western blotting, and transmission electron microscopy (TEM) to study ferroptosis in gastric cancer. The results revealed that silencing latent transforming growth factor β binding proteins (LTBP2) can significantly inhibit GC cell proliferation and decrease cellular GSH levels, reduce GPX4 activity, and increase ROS generation and malondialdehyde (MDA) levels, leading to ferroptosis in GC cells. In addition, we demonstrate that suppression of LTBP2 could regulate the p62-Keap1-Nrf2 pathway, thereby downregulating the GPX4 and xCT expression and upregulating the PTGS2 and 4HNE expression. Our findings described a new role of LTBP2 in regulating ferroptosis, which heralds the prospect of ferroptosis-mediated cancer therapy.
format Online
Article
Text
id pubmed-9371865
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-93718652022-08-12 LTBP2 Knockdown Promotes Ferroptosis in Gastric Cancer Cells through p62-Keap1-Nrf2 Pathway Wang, TingAn Zhou, ZiHan Wang, ChunMiao Qin, YuZhou Wu, Liucheng Hu, BangLi Jin, QinWen Wei, WeiYuan Huang, MingWei Biomed Res Int Research Article Gastric cancer (GC) is one of the most common gastrointestinal malignancies. Ferroptosis is a new type of peroxidation-driven and iron-dependent cell death. However, the biological functions and exact regulatory mechanisms of ferroptosis in GC remain elusive. Here, we performed RNAi and gene transfection, cell viability assay, lipid peroxidation assay, reactive oxygen species (ROS) assay, glutathione assay, qRT-PCR, Western blotting, and transmission electron microscopy (TEM) to study ferroptosis in gastric cancer. The results revealed that silencing latent transforming growth factor β binding proteins (LTBP2) can significantly inhibit GC cell proliferation and decrease cellular GSH levels, reduce GPX4 activity, and increase ROS generation and malondialdehyde (MDA) levels, leading to ferroptosis in GC cells. In addition, we demonstrate that suppression of LTBP2 could regulate the p62-Keap1-Nrf2 pathway, thereby downregulating the GPX4 and xCT expression and upregulating the PTGS2 and 4HNE expression. Our findings described a new role of LTBP2 in regulating ferroptosis, which heralds the prospect of ferroptosis-mediated cancer therapy. Hindawi 2022-08-04 /pmc/articles/PMC9371865/ /pubmed/35968244 http://dx.doi.org/10.1155/2022/6532253 Text en Copyright © 2022 TingAn Wang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, TingAn
Zhou, ZiHan
Wang, ChunMiao
Qin, YuZhou
Wu, Liucheng
Hu, BangLi
Jin, QinWen
Wei, WeiYuan
Huang, MingWei
LTBP2 Knockdown Promotes Ferroptosis in Gastric Cancer Cells through p62-Keap1-Nrf2 Pathway
title LTBP2 Knockdown Promotes Ferroptosis in Gastric Cancer Cells through p62-Keap1-Nrf2 Pathway
title_full LTBP2 Knockdown Promotes Ferroptosis in Gastric Cancer Cells through p62-Keap1-Nrf2 Pathway
title_fullStr LTBP2 Knockdown Promotes Ferroptosis in Gastric Cancer Cells through p62-Keap1-Nrf2 Pathway
title_full_unstemmed LTBP2 Knockdown Promotes Ferroptosis in Gastric Cancer Cells through p62-Keap1-Nrf2 Pathway
title_short LTBP2 Knockdown Promotes Ferroptosis in Gastric Cancer Cells through p62-Keap1-Nrf2 Pathway
title_sort ltbp2 knockdown promotes ferroptosis in gastric cancer cells through p62-keap1-nrf2 pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9371865/
https://www.ncbi.nlm.nih.gov/pubmed/35968244
http://dx.doi.org/10.1155/2022/6532253
work_keys_str_mv AT wangtingan ltbp2knockdownpromotesferroptosisingastriccancercellsthroughp62keap1nrf2pathway
AT zhouzihan ltbp2knockdownpromotesferroptosisingastriccancercellsthroughp62keap1nrf2pathway
AT wangchunmiao ltbp2knockdownpromotesferroptosisingastriccancercellsthroughp62keap1nrf2pathway
AT qinyuzhou ltbp2knockdownpromotesferroptosisingastriccancercellsthroughp62keap1nrf2pathway
AT wuliucheng ltbp2knockdownpromotesferroptosisingastriccancercellsthroughp62keap1nrf2pathway
AT hubangli ltbp2knockdownpromotesferroptosisingastriccancercellsthroughp62keap1nrf2pathway
AT jinqinwen ltbp2knockdownpromotesferroptosisingastriccancercellsthroughp62keap1nrf2pathway
AT weiweiyuan ltbp2knockdownpromotesferroptosisingastriccancercellsthroughp62keap1nrf2pathway
AT huangmingwei ltbp2knockdownpromotesferroptosisingastriccancercellsthroughp62keap1nrf2pathway