title: Parallel mRNA and microRNA profiling of HEV71-infected human neuroblastoma cells reveal the up-regulation of miR-1246 in association with DLG3 repression.
abstract: Human enterovirus 71 (HEV71) has emerged as the leading cause of viral encephalitis in children in most Asian countries. The roles of host miRNAs in the neurological pathogenesis of HEV71 infection remain unknown. In the present study, comprehensive miRNA expression profiling in HEV71-infected human neuroblastoma SH-SY5Y cells was performed using the Affymetrix Gene Chip microarray assay and was validated using real-time RT-PCR. Among the 69 differentially expressed miRNAs, miR-1246 was specifically induced by HEV71 infection in human neuroblastoma cells, but inhibition of miR-1246 failed to affect HEV71 replication. Parallel mRNA and microRNA profiling based on the 35 K Human Genome Array identified 182 differentially regulated genes. Target prediction of miR-1246 and network modeling revealed 14 potential target genes involved in cell death and cell signaling. Finally, a combined analysis of the results from mRNA profiling and miR-1246 target predication led to the identification of disc-large homolog 3 (DLG3), which is associated with neurological disorders, for further validation. Sequence alignment and luciferase reporter assay showed that miR-1246 directly bound with the 3'-UTR of DLG3 gene. Down-regulation of miR-1246 induced significant changes in DLG3 expression levels in HEV71-infected SHSY5Y cells. Together, these results suggested that miR-1246 might play a role in neurological pathogenesis of HEV71 by regulating DLG3 gene in infected cells. These findings provide new information on the miRNA and mRNA profiles of HEV71-infected neuroblastoma cells. The biological significance of miR-1246 and DLG3 during the course of HEV71 infection deserves further investigation.
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China; PLA 404 Hospital, Weihai, Shandong, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Xu
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Han
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Deng
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Shun-Ya
authors.initials: SY
authors.lastname: Zhu
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China; Graduate School, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Yue-Xiang
authors.initials: YX
authors.lastname: Li
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Qing-Gong
authors.initials: QG
authors.lastname: Nian
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wu
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: E-De
authors.initials: ED
authors.lastname: Qin
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China; Graduate School, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D029821:Enterovirus A, Human / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D017930:Genes, Reporter; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D025941:Protein Interaction Mapping; D016415:Sequence Alignment; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014709:Vero Cells
chemical_list: D020413:3' Untranslated Regions; C116869:DLG3 protein, human; C577700:MIRN1246 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D014157:Transcription Factors; D008156:Luciferases
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