Affiliation:
1. Department of Clinical Laboratory, The First Afliated Hospital of Kunming Medical University, Kunming, China
2. Yunnan Key Laboratory of Laboratory Medicine, Kunming, China
3. Yunnan Province Clinical Research Center for Laboratory Medicine, Kunming, China
4. School of Public Health, Kunming Medical University, Kunming, China
Abstract
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 IκBα, 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.
Funder
Yunnan Province “High level Talent Training Support Plan” - Youth Top Talents Project
National Natural Science Foundation of China
Department of Science and Technology of Yunnan Province - Basic Research Program - General Project
Scientific and technological Innovation team of KunmingMedical University
535 Talent Project of First Affiliated Hospital of Kunming Medical University
Funding Major Science and Technology Projects of Yunnan Privince/First Affiliated Hospitail of Kunming Medical University
“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