title: Hsa-let-7c-5p augments enterovirus 71 replication through viral subversion of cell signaling in rhabdomyosarcoma cells.
abstract: BACKGROUND
  Human enterovirus 71 (EV71) causes severe hand, foot and mouse disease, accompanied by neurological complications. During the interaction between EV71 and the host, the virus subverts host cell machinery for its own replication. However, the roles of microRNAs (miRNAs) in this process remain obscure.
  
  
  RESULTS
  In this study, we found that the miRNA hsa-let-7c-5p was significantly upregulated in EV71-infected rhabdomyosarcoma cells. The overexpression of hsa-let-7c-5p promoted replication of the virus, and the hsa-let-7c-5p inhibitor suppressed viral replication. Furthermore, hsa-let-7c-5p targeted mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and inhibited its expression. Interestingly, downregulation of MAP4K4 expression led to an increase in EV71 replication. In addition, MAP4K4 knockdown or transfection with the hsa-let-7c-5p mimic led to activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, whereas the hsa-let-7c-5p inhibitor inhibited activation of this pathway. Moreover, EV71 infection promoted JNK pathway activation to facilitate viral replication.
  
  
  CONCLUSIONS
  Our data suggested that hsa-let-7c-5p facilitated EV71 replication by inhibiting MAP4K4 expression, which might be related to subversion of the JNK pathway by the virus. These results may shed light on a novel mechanism underlying the defense of EV71 against cellular responses. In addition, these findings may facilitate the development of new antiviral strategies for use in future therapies.
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071 China ; Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 China.
authors.forename: Bingfei
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071 China.
authors.forename: Min
authors.initials: M
authors.lastname: Chu
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071 China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071 China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071 China.
authors.forename: Yongjuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071 China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071 China.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071 China.
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071 China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071 China ; Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 China.
authors.forename: Biwen
authors.initials: B
authors.lastname: Peng
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071 China ; Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: He
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071 China ; Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 China.
authors.forename: Wanhong
authors.initials: W
authors.lastname: Liu
keywords: EV71; Hsa-let-7c-5p; JNK; MAP4K4