title: MicroRNA-1 and microRNA-206 suppress LXRα-induced lipogenesis in hepatocytes.
abstract: Liver X receptor α (LXRα) plays a critical role in the transcriptional control of lipid metabolism. LXR activation induces the expression of lipogenic genes, which promote hepatic steatosis and steatohepatitis. However, the regulation of LXR is not fully understood. MicroRNAs (miRs) are regarded as important negative regulators of gene expression. In this study, we found that miR-1/miR-206 repressed LXRα-induced accumulation of lipid droplets in hepatocytes. In addition, bioinformatic analysis predicted a same putative target-site for miR-1/miR-206 located within the 3'-untranslated region (3'-UTR) of LXRα mRNA. The reporter assay revealed that miR-1/miR-206 directly targeted the 3'-UTR of LXRα mRNA. Furthermore, miR-1/miR-206 repressed LXRα expression at both mRNA and protein levels, accompanied with the inhibition of expression of LXRα target genes, such as sterol-regulatory element binding protein 1c, fatty acid synthase, carbohydrate responsive element-binding protein and acetyl-CoA carboxylase 1, which are important effectors of LXRα implicated in lipogenesis. Moreover, ectopic expression of LXRα without the 3'-UTR dramatically attenuated the miR-1/miR-206-induced decrease of lipogenic genes and lipid droplet accumulation. Taken together, we for the first time demonstrated that miR-1/miR-206 attenuated LXRα-induced lipogenesis by targeting the 3'-UTR of LXRα mRNA, suggesting that miR-1/miR-206-LXRα pathway may be a novel target for the treatment of lipogenesis-associated diseases.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhong
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yijun
authors.initials: Y
authors.lastname: Zeng
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Xu
authors.forename: Yuanyin
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xie
authors.initials: X
authors.lastname: He
authors.forename: Fengtian
authors.initials: F
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D015536:Down-Regulation; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D050155:Lipogenesis / Q000235:genetics; D000071518:Liver X Receptors; D035683:MicroRNAs / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000071518:Liver X Receptors; C544547:MIRN1 microRNA, human; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger