Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532-3p/Acyl-CoA oxidase 1(ACOX1) pathway

Chuanhai Li; Lidan Jiang; Yuan Jin; Donghui Zhang; Jing Chen; Yuan Qi; Rongrong Fan; Jiao Luo; Lin Xu; Wanli Ma; Kunming Zhao; Dianke Yu

doi:10.1016/j.ecoenv.2021.113011

Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532-3p/Acyl-CoA oxidase 1(ACOX1) pathway

Ecotoxicol Environ Saf. 2021 Nov 24:228:113011. doi: 10.1016/j.ecoenv.2021.113011. Online ahead of print.

Authors

Chuanhai Li¹, Lidan Jiang¹, Yuan Jin¹, Donghui Zhang¹, Jing Chen¹, Yuan Qi¹, Rongrong Fan¹, Jiao Luo¹, Lin Xu¹, Wanli Ma¹, Kunming Zhao¹, Dianke Yu²

Affiliations

¹ School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China.
² School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China. Electronic address: dianke.yu@qdu.edu.cn.

PMID: 34837870
DOI: 10.1016/j.ecoenv.2021.113011

Abstract

6:2 Chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an alternative product of perfluorooctane sulfonate (PFOS), has been frequently detected in various environmental, wildlife, and human samples. A few studies revealed the hepatotoxicity of 6:2 Cl-PFESA in animals, but the underlying toxicity mechanisms remain largely unknown. In this study, we investigated the lipid metabolism disorders of 6:2 Cl-PFESA through miRNA-gene interaction mode in Huh-7 cells. Our results showed that 6:2 Cl-PFESA significantly promoted cellular lipid accumulation and increased the expression of Acyl-CoA oxidase 1 (ACOX1), with the lowest effective concentrations (LOECs) of 3 μM. In silico analysis showed that hsa-miR-532-3p is a potential miRNA molecule targeting ACOX1. Fluorescent-based RNA electrophoretic mobility shift assay (FREMSA) and ACOX1-mediated luciferase reporter gene assays showed that hsa-miR-532-3p could directly bind to ACOX1 and inhibit its transcription activity. Besides, 6:2 Cl-PFESA decreased the expression of hsa-miR-532-3p in the PPARα-independent manner. Overexpression of hsa-miR-532-3p promoted 6:2 Cl-PFESA-induced cellular lipid accumulation and decreased the ACOX1 production in Huh-7 cells. Taken together, at human exposure relevant concentrations, 6:2 Cl-PFESA might upregulate the expression levels of ACOX1 through downregulating hsa-miR-532-3p, and disturbed lipid homeostasis in Huh-7 cells, which revealed a novel epigenetic mechanism of 6:2 Cl-PFESA-induced hepatic lipid toxic effects.

Keywords: 6:2 Cl-PFESA; ACOX1; Hsa-miR-532–3p; Lipid metabolism disorders.