Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532–3p/Acyl-CoA oxidase 1(ACOX1) pathway
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 tox...
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Elsevier
2021
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oai:doaj.org-article:2755bc03da064ef2aca92a90935f02c22021-11-26T04:23:17ZLipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532–3p/Acyl-CoA oxidase 1(ACOX1) pathway0147-651310.1016/j.ecoenv.2021.113011https://doaj.org/article/2755bc03da064ef2aca92a90935f02c22021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321011234https://doaj.org/toc/0147-65136:2 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.Chuanhai LiLidan JiangYuan JinDonghui ZhangJing ChenYuan QiRongrong FanJiao LuoLin XuWanli MaKunming ZhaoDianke YuElsevierarticle6:2 Cl-PFESAHsa-miR-532–3pACOX1Lipid metabolism disordersEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 228, Iss , Pp 113011- (2021) |
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6:2 Cl-PFESA Hsa-miR-532–3p ACOX1 Lipid metabolism disorders Environmental pollution TD172-193.5 Environmental sciences GE1-350 |
| spellingShingle |
6:2 Cl-PFESA Hsa-miR-532–3p ACOX1 Lipid metabolism disorders Environmental pollution TD172-193.5 Environmental sciences GE1-350 Chuanhai Li Lidan Jiang Yuan Jin Donghui Zhang Jing Chen Yuan Qi Rongrong Fan Jiao Luo Lin Xu Wanli Ma Kunming Zhao Dianke Yu Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532–3p/Acyl-CoA oxidase 1(ACOX1) pathway |
| description |
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. |
| format |
article |
| author |
Chuanhai Li Lidan Jiang Yuan Jin Donghui Zhang Jing Chen Yuan Qi Rongrong Fan Jiao Luo Lin Xu Wanli Ma Kunming Zhao Dianke Yu |
| author_facet |
Chuanhai Li Lidan Jiang Yuan Jin Donghui Zhang Jing Chen Yuan Qi Rongrong Fan Jiao Luo Lin Xu Wanli Ma Kunming Zhao Dianke Yu |
| author_sort |
Chuanhai Li |
| title |
Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532–3p/Acyl-CoA oxidase 1(ACOX1) pathway |
| title_short |
Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532–3p/Acyl-CoA oxidase 1(ACOX1) pathway |
| title_full |
Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532–3p/Acyl-CoA oxidase 1(ACOX1) pathway |
| title_fullStr |
Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532–3p/Acyl-CoA oxidase 1(ACOX1) pathway |
| title_full_unstemmed |
Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532–3p/Acyl-CoA oxidase 1(ACOX1) pathway |
| title_sort |
lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through hsa-mirna-532–3p/acyl-coa oxidase 1(acox1) pathway |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/2755bc03da064ef2aca92a90935f02c2 |
| work_keys_str_mv |
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