miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα–Srebp1 pathway in the marine teleost Siganus canaliculatus
miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα–Srebp1 pathway in the marine teleost Siganus canaliculatus
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miR-26a 通过靶向海洋硬骨鱼 Siganus canaliculatus 中的 Lxrα-Srebp1 途径介导 LC-PUFA 生物合成
DOI：
10.1074/jbc.ra120.014858
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发表时间：
2020-08
影响因子：
4.8
通讯作者：
Yuanyou Li
中科院分区：
文献类型：
--
作者：
Cuiying Chen;Shuqi Wang;Yu Hu;Mei Zhang;Xi;a He;Cuihong You;Xiaobo Wen;Óscar Monroig;Douglas R. Tocher;Yuanyou Li
最近已经证明microRNA是脂质代谢的重要调节剂。然而，microRNA介导的调节脊椎动物中长链多不饱和脂肪酸（LC-PUFA）生物合成的机制在很大程度上仍然未知。在此，我们首次探讨了miR-26 a在长沟篮子鱼LC-PUFA生物合成中的作用。结果表明，微咸水养殖的兔鱼肝脏中miR-26 a表达显著下调，而在海水养殖的中华绒螯蟹中miR-26 a表达显著下调。用LC-PUFA前体α-亚麻酸孵育的小管肝细胞系（SCHL）中发现，miR-26 a可能参与LC-PUFA的生物合成，因为其丰度受影响LC-PUFA生物合成的因素调节。在与α-亚麻酸孵育的SCHL细胞中，在肝X受体α（lxrα）和固醇调节元件结合蛋白-1（srebp 1）以及LC-PUFA生物合成相关基因（Δ4 fads 2、Δ6Δ5 fads 2和elovl 5）的表达中观察到相反的模式。荧光素酶报告基因分析显示，兔鱼lxrα是miR-26 a的靶点，SCHL细胞中miR-26 a的过表达显著降低了激动剂T0901317诱导的Lxrα、Srebp 1和Δ6Δ5 Fads 2的蛋白水平。此外，通过敲低miR-26 a增加内源性Lxrα促进了Srebp 1激活，并伴随着参与LC-PUFA生物合成的基因表达增加，从而促进了体外和体内LC-PUFA生物合成。这些结果表明miR-26 a通过靶向Lxrα-Srebp 1途径在调节LC-PUFA生物合成中起关键作用，并为脊椎动物中控制LC-PUFA生物合成和积累的调控网络提供了新的见解。
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.
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DOI：
--
发表时间：
2012
期刊：
--
影响因子：
--
作者：
Ó. Monroig;Shuqi Wang;Liang Zhang;C. You;D. Tocher;Yuanyou Li
通讯作者：
Ó. Monroig;Shuqi Wang;Liang Zhang;C. You;D. Tocher;Yuanyou Li
影响因子：
1.9
作者：
H. Sprecher;Qi Chen;F. Q. Yin
通讯作者：
H. Sprecher;Qi Chen;F. Q. Yin
DOI：
10.1016/j.bbalip.2014.03.009
发表时间：
2014-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Qinghao Zhang;Dizhi Xie;Shuqi Wang;C. You;Ó. Monroig;D. Tocher;Yuanyou Li
通讯作者：
Qinghao Zhang;Dizhi Xie;Shuqi Wang;C. You;Ó. Monroig;D. Tocher;Yuanyou Li
DOI：
10.1073/pnas.1630797100
发表时间：
2003-08-19
影响因子：
11.1
作者：
Zeng, Y;Yi, R;Cullen, BR
通讯作者：
Cullen, BR
影响因子：
4.5
作者：
Tocher, Douglas R.
通讯作者：
Tocher, Douglas R.