LncRNA PU.1 AS regulates arsenic-induced lipid metabolism through EZH2/Sirt6/SREBP-1c pathway.

Author(s) Dong, Z.; Li, C.; Yin, C.; Xu, M.; Liu, S.; Gao, M.
Journal J Environ Sci (China)
Date Published 2019 Nov
Abstract

Arsenic (As) is an omnipresent metalloid toxicant, which has elicited serious environmental pollution and health risky problems. Previous studies have uncovered that the As exposure could also cause markedly reduction of serum triglycerides in mice. However, the regulation mechanisms are still largely unknown. The present study is aimed to elucidate the molecular mechanisms of lncRNAs in As-induced lipid metabolic disequilibrium. We demonstrated that lncRNA PU.1 AS was significantly induced in the liver of As-feed mice companied with lower serum triglycerides contents; further in vitro experiment confirmed that PU.1 AS regulated liver cells lipid accumulation by nile red fluorescence staining. Intensive mechanistic investigations illustrated that PU.1 AS could interact with EZH2 protein to regulate its downstream target gene expression, and As-induced PU.1 AS attenuated EZH2-supppressed Sirt6 expression, thereafter leading to a decreased SREBP-1c protein expression, as well as the diminished synthesis of triglycerides in hepatocytes. In conclusion, this study provided a new lncRNA-related regulatory signaling pathway participating in As-induced abnormal lipid metabolism.

DOI 10.1016/j.jes.2019.05.019
ISSN 1001-0742
Citation Dong Z, Li C, Yin C, Xu M, Liu S, Gao M. LncRNA PU.1 AS regulates arsenic-induced lipid metabolism through EZH2/Sirt6/SREBP-1c pathway. J Environ Sci (China). 2019;85:138-146.