Bromodomain and WD-repeat domain-containing protein 3 (BRWD3) exhibits high expression in lung adenocarcinoma (LUAD) tissues and cells; however, its function in arsenic-induced toxicological responses remains unclear. This study aimed to investigate BRWD3 expression in response to arsenic-induced conditions and its impact on the proliferation and apoptosis of LUAD cell line SPC-A1 upon BRWD3 knockdown. The results revealed a decrease in BRWD3 expression in SPC-A1 cells treated with sodium arsenite (NaAsO2), but not sodium arsenite's metabolites. BRWD3 knockdown suppressed cell proliferation and induced apoptosis in SPC-A1 cells. Western blot analysis revealed that BRWD3 knockdown resulted in the upregulation of p53, phospho-p53-Ser392, and its downstream factors including MDM2, Bak, and Bax. Additionally, we observed the downregulation of p65, phospho-p65-Ser276, phospho-p65-Ser536, and its downstream factors, including I kappa B alpha, BIRC3, XIAP and CIAP1. Moreover, polymerase chain reaction analysis showed that BRWD3 knockdown also resulted in the downregulation of proliferation-related genes and upregulation of apoptosis-related genes. In conclusion, BRWD3 mediated proliferation and apoptosis via the p53 and p65 pathways in response to arsenic exposure, suggesting potential implications for LUAD treatment through BRWD3 downregulation by arsenic.
基金:
National Natural Science Foundation of China [81660388]; Department of Science and Technology of Yunnan Province - Basic Research Program-General Project [202101AT070223]; The "High-level Talents Training Support Program" of Yunnan Province-Project for Young Top Talents; Training Program for Leaders of Medical Disciplines of Yunnan Provincial Health Commission [D-2018024]; First Affiliated Hospital of Kunming Medical University [2023535D08]; Yunnan Province "High level Talent Training Support Plan"- Youth Top Talents Project [YNWR-QNBJ-2019-159]; Funding Major Science and Technology Projects of Yunnan Privince/First Affiliated Hospitail of Kunming Medical University [2023zdpy05]; Scientific and technological Innovation team of Kunming Medical University [CXTD202201]
第一作者机构:[1]Kunming Med Univ, Dept Clin Lab, Affiliated Hosp 1, 295 Xichang Rd, Kunming, Yunnan, Peoples R China[2]Yunnan Key Lab Lab Med, Kunming, Peoples R China[3]Yunnan Prov Clin Res Ctr Lab Med, Kunming, Peoples R China
通讯作者:
通讯机构:[1]Kunming Med Univ, Dept Clin Lab, Affiliated Hosp 1, 295 Xichang Rd, Kunming, Yunnan, Peoples R China[2]Yunnan Key Lab Lab Med, Kunming, Peoples R China[3]Yunnan Prov Clin Res Ctr Lab Med, Kunming, Peoples R China
推荐引用方式(GB/T 7714):
Zhu Yanhua,Xiao Mei,Zhao Ruihuan,et al.Arsenic-induced downregulation of BRWD3 suppresses proliferation and induces apoptosis in lung adenocarcinoma cells through the p53 and p65 pathways[J].HUMAN & EXPERIMENTAL TOXICOLOGY.2024,43:doi:10.1177/09603271241279166.
APA:
Zhu, Yanhua,Xiao, Mei,Zhao, Ruihuan,Yang, Xuefei,Wu, Kun...&Zhang, Yanliang.(2024).Arsenic-induced downregulation of BRWD3 suppresses proliferation and induces apoptosis in lung adenocarcinoma cells through the p53 and p65 pathways.HUMAN & EXPERIMENTAL TOXICOLOGY,43,
MLA:
Zhu, Yanhua,et al."Arsenic-induced downregulation of BRWD3 suppresses proliferation and induces apoptosis in lung adenocarcinoma cells through the p53 and p65 pathways".HUMAN & EXPERIMENTAL TOXICOLOGY 43.(2024)