title: MicroRNA-22 negatively regulates poly(I:C)-triggered type I interferon and inflammatory cytokine production via targeting mitochondrial antiviral signaling protein (MAVS).
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in regulating the host immune response. Here we found that miR-22 is induced in glial cells upon stimulation with poly(I:C). Overexpression of miR-22 in the cultured cells resulted in decreased activity of interferon regulatory factor-3 and nuclear factor-kappa B, which in turn led to reduced expression of interferon-β and inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and chemokine (C-C motif) ligand 5, upon stimulation with poly(I:C), whereas knockdown of miR-22 had the opposite effect. We used a combination of bioinformatics and experimental techniques to demonstrate that mitochondrial antiviral signaling protein (MAVS), which positively regulates type I interferon production, is a novel target of miR-22. Overexpression of miR-22 decreased the activity of a luciferase reporter containing the MAVS 3'-untranslated region and led to decreased MAVS mRNA and protein levels. In contrast, ectopic expression of miR-22 inhibitor led to elevated MAVS expression. Collectively, our results demonstrate that miR-22 negatively regulates poly(I:C)-induced production of type I interferon and inflammatory cytokines via targeting MAVS.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.
authors.forename: Shengfeng
authors.initials: S
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.
authors.forename: Usama
authors.initials: U
authors.lastname: Ashraf
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.
authors.forename: Ali
authors.initials: A
authors.lastname: Zohaib
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.
authors.forename: Bibo
authors.initials: B
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.
authors.forename: Yunchuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.|The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China.
authors.forename: Shengbo
authors.initials: S
authors.lastname: Cao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004664:Encephalitis Virus, Japanese; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007370:Interferon Type I / Q000096:biosynthesis*; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D018836:Inflammation Mediators; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; C505371:MAVS protein, human; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D011070:Poly I-C
keywords: MAVS; inflammatory cytokines; miR-22; poly(I:C); type I interferon