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-26a in LC-PUFA biosynthesis in the marine rabbitfishSiganus canaliculatus. The results showed that miR-26a was significantly down-regulated in liver of rabbitfish reared in brackish water and inS. canaliculatushepatocyte line (SCHL) incubated with the LC-PUFA precursor alpha-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 alpha (lxr alpha) and sterol regulatory element-binding protein-1 (srebp1), as well as the LC-PUFA biosynthesis-related genes (Delta 4fads2, Delta 6 Delta 5fads2, andelovl5) in SCHL cells incubated with alpha-linolenic acid. Luciferase reporter assays revealed rabbitfishlxr alpha as a target of miR-26a, and overexpression of miR-26a in SCHL cells markedly reduced protein levels of Lxr alpha, Srebp1, and Delta 6 Delta 5 Fads2 induced by the agonist T0901317. Moreover, increasing endogenous Lxr alpha 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 bothin vitroandin vivo. These results indicate a critical role of miR-26a in regulating LC-PUFA biosynthesis through targeting the Lxr alpha-Srebp1 pathway and provide new insights into the regulatory network controlling LC-PUFA biosynthesis and accumulation in vertebrates.