miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα-Srebp1 pathway in the marine teleost Siganus canaliculatus

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-26...

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Detalles Bibliográficos
Autores: Chen, Cuiying, Wang, Shuqi, Hu, Yu, Zhang, Mei, He, Xianda, You, Cuihong, Wen, Xiaobo, Monroig, Óscar, Tocher, Douglas R., Li, Yuanyou
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/225101
Acceso en línea:http://hdl.handle.net/10261/225101
Access Level:acceso abierto
Palabra clave:miR-26a
Lxrα
Srebp1
LC-PUFA
Biosynthesis
Siganus canaliculatus
MicroRNA (miRNA)
Fatty acid
Gene regulation
Fatty acid metabolism
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oai_identifier_str oai:digital.csic.es:10261/225101
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repository_id_str
spelling miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα-Srebp1 pathway in the marine teleost Siganus canaliculatusChen, CuiyingWang, ShuqiHu, YuZhang, MeiHe, XiandaYou, CuihongWen, XiaoboMonroig, ÓscarTocher, Douglas R.Li, YuanyoumiR-26aLxrαSrebp1LC-PUFABiosynthesisSiganus canaliculatusMicroRNA (miRNA)Fatty acidGene regulationFatty acid metabolismMicroRNAs 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.This work was financially supported by National Natural Science Foundation of China Grants 31873040 and 31702357, National Key R&D Program of China Grant 2018YFD0900400, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding Grant 2017B030314058, and The Shantou University (STU) Scientific Research Foundation for Talents Grant NTF19019.American Society for Biochemistry and Molecular BiologyNational Natural Science Foundation of ChinaNational Key Research and Development Program (China)Natural Science Foundation of Guangdong ProvinceMonroig, Óscar [0000-0001-8712-0440]Tocher, Douglas R. [0000-0002-8603-9410]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020202020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/225101reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1074/jbc.RA120.014858Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2251012026-05-22T06:33:51Z
dc.title.none.fl_str_mv miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα-Srebp1 pathway in the marine teleost Siganus canaliculatus
title miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα-Srebp1 pathway in the marine teleost Siganus canaliculatus
spellingShingle miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα-Srebp1 pathway in the marine teleost Siganus canaliculatus
Chen, Cuiying
miR-26a
Lxrα
Srebp1
LC-PUFA
Biosynthesis
Siganus canaliculatus
MicroRNA (miRNA)
Fatty acid
Gene regulation
Fatty acid metabolism
title_short miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα-Srebp1 pathway in the marine teleost Siganus canaliculatus
title_full miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα-Srebp1 pathway in the marine teleost Siganus canaliculatus
title_fullStr miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα-Srebp1 pathway in the marine teleost Siganus canaliculatus
title_full_unstemmed miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα-Srebp1 pathway in the marine teleost Siganus canaliculatus
title_sort miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα-Srebp1 pathway in the marine teleost Siganus canaliculatus
dc.creator.none.fl_str_mv Chen, Cuiying
Wang, Shuqi
Hu, Yu
Zhang, Mei
He, Xianda
You, Cuihong
Wen, Xiaobo
Monroig, Óscar
Tocher, Douglas R.
Li, Yuanyou
author Chen, Cuiying
author_facet Chen, Cuiying
Wang, Shuqi
Hu, Yu
Zhang, Mei
He, Xianda
You, Cuihong
Wen, Xiaobo
Monroig, Óscar
Tocher, Douglas R.
Li, Yuanyou
author_role author
author2 Wang, Shuqi
Hu, Yu
Zhang, Mei
He, Xianda
You, Cuihong
Wen, Xiaobo
Monroig, Óscar
Tocher, Douglas R.
Li, Yuanyou
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv National Natural Science Foundation of China
National Key Research and Development Program (China)
Natural Science Foundation of Guangdong Province
Monroig, Óscar [0000-0001-8712-0440]
Tocher, Douglas R. [0000-0002-8603-9410]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv miR-26a
Lxrα
Srebp1
LC-PUFA
Biosynthesis
Siganus canaliculatus
MicroRNA (miRNA)
Fatty acid
Gene regulation
Fatty acid metabolism
topic miR-26a
Lxrα
Srebp1
LC-PUFA
Biosynthesis
Siganus canaliculatus
MicroRNA (miRNA)
Fatty acid
Gene regulation
Fatty acid metabolism
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/225101
url http://hdl.handle.net/10261/225101
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1074/jbc.RA120.014858
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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