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Título: | miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα-Srebp1 pathway in the marine teleost Siganus canaliculatus |
Autor: | Chen, Cuiying; Wang, Shuqi; Hu, Yu; Zhang, Mei; He, Xianda; You, Cuihong; Wen, Xiaobo; Monroig, Óscar CSIC ORCID; Tocher, Douglas R.; Li, Yuanyou | Palabras clave: | miR-26a Lxrα Srebp1 LC-PUFA Biosynthesis Siganus canaliculatus MicroRNA (miRNA) Fatty acid Gene regulation Fatty acid metabolism |
Fecha de publicación: | 2-oct-2020 | Editor: | American Society for Biochemistry and Molecular Biology | Citación: | Journal of Biological Chemistry 295: 13875-13886 (2020) | Resumen: | MicroRNAs have been recently shown to be important regulators of lipid metabolism. However, the mechanisms of microRNA-mediated regulation of long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis in vertebrates remain largely unknown. Herein, we for the first time addressed the role of miR-26a in LC-PUFA biosynthesis in the marine rabbitfish Siganus canaliculatus The results showed that miR-26a was significantly down-regulated in liver of rabbitfish reared in brackish water and in S. canaliculatus hepatocyte line (SCHL) incubated with the LC-PUFA precursor α-linolenic acid, suggesting that miR-26a may be involved in LC-PUFA biosynthesis because of its abundance being regulated by factors affecting LC-PUFA biosynthesis. Opposite patterns were observed in the expression of liver X receptor α (lxrα) and sterol regulatory element-binding protein-1 (srebp1), as well as the LC-PUFA biosynthesis-related genes (Δ4 fads2, Δ6Δ5 fads2, and elovl5) in SCHL cells incubated with α-linolenic acid. Luciferase reporter assays revealed rabbitfish lxrα as a target of miR-26a, and overexpression of miR-26a in SCHL cells markedly reduced protein levels of Lxrα, Srebp1, and Δ6Δ5 Fads2 induced by the agonist T0901317. Moreover, increasing endogenous Lxrα by knockdown of miR-26a facilitated Srebp1 activation and concomitant increased expression of genes involved in LC-PUFA biosynthesis and consequently promoted LC-PUFA biosynthesis both in vitro and in vivo These results indicate a critical role of miR-26a in regulating LC-PUFA biosynthesis through targeting the Lxrα-Srebp1 pathway and provide new insights into the regulatory network controlling LC-PUFA biosynthesis and accumulation in vertebrates. | Versión del editor: | http://dx.doi.org/10.1074/jbc.RA120.014858 | URI: | http://hdl.handle.net/10261/225101 | DOI: | 10.1074/jbc.RA120.014858 | Identificadores: | doi: 10.1074/jbc.RA120.014858 issn: 0021-9258 e-issn: 1083-351X |
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