ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2023; 14(8):1309-1320. doi:10.7150/jca.84036 This issue Cite
Research Paper
CHAC2 promotes lung adenocarcinoma by regulating ROS-mediated MAPK pathway activation
1. Department of Thoracic Surgery, the Second Xiangya Hospital of Central South University, 410011, Changsha, China.
2. Department of Respiratory Medicine, the First Hospital of ChangSha, 410011, Changsha, China.
Abstract
An imbalance in ROS (reactive oxidative species) and the antioxidant barrier regulates the process of tumorigenesis. GSH has a key effect in preventing cells from oxidative damage by scavenging ROS. The role of CHAC2, an enzyme regulating GSH, in lung adenocarcinoma remains unknown. Here, RNA sequencing data analysis and immunohistochemistry (IHC) assays of lung adenocarcinoma and normal lung tissues were used to verify the expression of CHAC2. The effect of CHAC2 on the proliferation abilities of lung adenocarcinoma cells was examined using a series of overexpression or knockout assays. RNA sequencing and IHC results showed that the expression level of CHAC2 in lung adenocarcinoma was higher than that in normal lung tissues. CCK-8, colony formation and subcutaneous xenograft experiments in BALB/c nude mice showed that in vitro and in vivo CHAC2 promoted the growth capacity of lung adenocarcinoma cells. Subsequent immunoblot, immunohistochemistry and flow cytometry experiments showed that CHAC2 increased ROS by reducing GSH in lung adenocarcinoma and that the elevated ROS activated the MAPK pathway. Our investigation identified a new role for CHAC2 and elucidated the mechanism by which CHAC2 promotes lung adenocarcinoma progression.
Keywords: lung adenocarcinoma (LUAD), cation transport regulator homolog 2 (CHAC2), reactive oxidative species (ROS), reduced glutathione (GSH)
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