MicroRNA-22 negatively regulates poly(I:C)-triggered type I interferon and inflammatory cytokine production via targeting mitochondrial antiviral signaling protein (MAVS)

// Shengfeng Wan 1, 2, 3, * , Usama Ashraf 1, 2, 3, * , Jing Ye 1, 2, 3 , Xiaodong Duan 1, 2, 3 , Ali Zohaib 1, 2, 3 , Wentao Wang 1, 2, 3 , Zheng Chen 1, 2, 3 , Bibo Zhu 1, 2, 3 , Yunchuan Li 1, 2, 3 , Huanchun Chen 1, 2, 3 , Shengbo Cao 1, 2, 3 1 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China 2 Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China 3 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, 430070, P. R. China * These authors contributed equally to this work Correspondence to: Shengbo Cao, email: sbcao@mail.hzau.edu.cn Keywords: miR-22, poly(I:C), type I interferon, inflammatory cytokines, MAVS Received: March 19, 2016 Accepted: September 25, 2016 Published: October 01, 2016 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.