PMID- 27285980 OWN - NLM STAT- MEDLINE DCOM- 20180213 LR - 20201209 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 31 DP - 2016 Aug 2 TI - MiR674 inhibits the neuraminidase-stimulated immune response on dendritic cells via down-regulated Mbnl3. PG - 48978-48994 LID - 10.18632/oncotarget.9832 [doi] AB - Neuraminidase (NA), a structural protein of the H9N2 avian influenza virus (H9N2 AIV), can facilitate viral invasion of the upper airway by cleaving the sialic acid moieties on mucin. Dendritic cells (DCs) are major antigen-presenting cells whose immune functions, such as presenting antigens and activating lymphocytes, can be regulated by microRNAs. Here, we studied the molecular mechanism of miRNA-induced repression of immune responses in mouse DCs. First, we screened for and verified the miRNAs induced by NA. Then, we showed that, consistent with the H9N2 virus treatment, the viral NA up-regulated the expression of miR-155, miR-674, and miR-499 in DCs; however, unlike H9N2 virus treatment, the presence of NA was associated with reduced expression of miR-181b1. Our results suggest that NA significantly increased DC surface markers CD80 and MHCII and enhanced the ability of activating lymphocytes and secreting cytokines compared with HA, NP and M2. Meanwhile, we found that miR-674 and miR-155 over-expression increased all surface markers of DC. Nevertheless, by inhibiting the expression of miR-674 and miR-155, NA lost the ability to promote DC maturation. Furthermore, we predicted and demonstrated that Pgm2l1, Aldh18a1, Camk1d, and Mbnl3 were the target genes of miR-674. Among them, Mbnl3 interference strongly blocked the mature DCs. Collectively, our data shed new light on the roles of and mechanisms involved in the repression of DCs by miRNAs, which may contribute to efforts to develop a prophylaxis for the influenza virus. FAU - Lin, Jian AU - Lin J AD - Life Science College, Nanjing Agricultural University, Weigang, Nanjing, Jiangsu, PR China. FAU - Chen, Ya T AU - Chen YT AD - Life Science College, Nanjing Agricultural University, Weigang, Nanjing, Jiangsu, PR China. FAU - Xia, Jing AU - Xia J AD - Life Science College, Nanjing Agricultural University, Weigang, Nanjing, Jiangsu, PR China. FAU - Yang, Qian AU - Yang Q AD - College of Veterinary Medicine, Nanjing Agricultural University, Weigang, Jiangsu, PR China. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Carrier Proteins) RN - 0 (Cytokines) RN - 0 (MBNL3 protein, mouse) RN - 0 (MIRN674 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Mirn155 microRNA, mouse) RN - 0 (RNA-Binding Proteins) RN - EC 3.2.1.18 (Neuraminidase) SB - IM MH - Animals MH - Antigen-Presenting Cells/immunology MH - Carrier Proteins/*metabolism MH - Cell Proliferation MH - Cytokines/metabolism MH - Dendritic Cells/*immunology MH - Down-Regulation MH - Gene Silencing MH - HEK293 Cells MH - Humans MH - Immune System MH - Influenza A Virus, H9N2 Subtype MH - Lentivirus MH - Lymphocyte Culture Test, Mixed MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - MicroRNAs/*metabolism MH - Neuraminidase/*metabolism MH - Phenotype MH - Polymerase Chain Reaction MH - RNA-Binding Proteins PMC - PMC5226485 OTO - NOTNLM OT - Immune response OT - Immunity OT - Immunology and Microbiology Section OT - dendritic cells OT - immune regulation OT - miR-674 OT - neuraminidase OT - virus replication COIS- There is no conflict of interest. EDAT- 2016/06/11 06:00 MHDA- 2018/02/14 06:00 PMCR- 2016/08/02 CRDT- 2016/06/11 06:00 PHST- 2015/11/01 00:00 [received] PHST- 2016/05/02 00:00 [accepted] PHST- 2016/06/11 06:00 [pubmed] PHST- 2018/02/14 06:00 [medline] PHST- 2016/06/11 06:00 [entrez] PHST- 2016/08/02 00:00 [pmc-release] AID - 9832 [pii] AID - 10.18632/oncotarget.9832 [doi] PST - ppublish SO - Oncotarget. 2016 Aug 2;7(31):48978-48994. doi: 10.18632/oncotarget.9832.