title: miR-709 modulates LPS-induced inflammatory response through targeting GSK-3β.
abstract: MicroRNAs (miRNAs) are endogenous small non-coding RNAs which modulate gene expression at the post-transcriptional level by either translational inhibition or mRNA degradation. MicroRNAs play important roles in both innate and adaptive immune response, including TLR-triggered immune response. In this study, we found that the expression of miR-709 was up-regulated in primary macrophage and RAW264.7 cells during the stimulation of LPS. Overexpression of miR-709 in RAW264.7 cells led to reduced production and gene expression of inflammatory cytokines (IL-6, TNF-α, IL-1β) during activation by LPS, whereas knockdown of miR-709 had completely opposite effects. We used bioinformatics and experimental techniques to demonstrate that GSK-3β is a direct target of miR-709. miR-709 mimics decreased GSK-3β protein but not mRNA level. We also found that miR-709 regulated the LPS-induced inflammatory response by targeting GSK-3β and elevating β-catenin. In conclusion, our data revealed a novel role for miR-709 in regulation of inflammatory response by targeting GSK-3β.
authors.affiliation: State Key laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China.
authors.forename: Hu
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China.
authors.forename: Luxi
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China.
authors.forename: Yaosheng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China. Electronic address: modelin@mail.sysu.edu.cn.
authors.forename: Delin
authors.initials: D
authors.lastname: Mo
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate / Q000235:genetics; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D000067996:RAW 264.7 Cells; D034741:RNA, Small Interfering / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; C000612385:MIRN709 microRNA, mouse; D035683:MicroRNAs; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta
keywords: GSK-3β; Inflammatory response; miR-709; β-Catenin