MicroRNA-22 negatively regulates poly(I:C)-triggered type I interferon and inflammatory cytokine production via targeting mitochondrial antiviral signaling protein (MAVS)
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Shengfeng Wan1,2,3,*, Usama Ashraf1,2,3,*, Jing Ye1,2,3, Xiaodong Duan1,2,3, Ali Zohaib1,2,3, Wentao Wang1,2,3, Zheng Chen1,2,3, Bibo Zhu1,2,3, Yunchuan Li1,2,3, Huanchun Chen1,2,3, Shengbo Cao1,2,3
1State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China
2Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China
3The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China
*These authors contributed equally to this work
Shengbo Cao, email: [email protected]
Keywords: miR-22, poly(I:C), type I interferon, inflammatory cytokines, MAVS
Received: March 19, 2016 Accepted: September 25, 2016 Published: October 01, 2016
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.
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