Dataset Information

MicroRNA-1202 plays a vital role in osteoarthritis via KCNQ1OT1 has-miR-1202-ETS1 regulatory pathway.

ABSTRACT: This study aimed to explore the molecular mechanism of osteoarthritis (OA) and provide information about new genes as potential targets for OA treatment. Gene expression profile of GSE105027, including 12 OA serum samples (OA group) and 12 healthy serum samples (ctrl group), was downloaded. The differentially expressed miRNAs (DEMs) as well as miRNA-mRNAs interactions were investigated, followed by function and pathway investigation. Then the protein-protein interaction (PPI) network was performed. Furthermore, the long non-coding RNA (lncRNA)-miRNA-mRNA interactions (competing endogenous RNAs, ceRNAs) were investigated. A total of 17 downregulated miRNAs were revealed between OA and ctrl groups. These DEMs such as has-miR-1202 were mainly enriched in GO functions like histone acetyltransferase binding and KEGG pathways like cellular senescence. The integrated PPI network analysis showed that has-miR-1202, has-miR-33b-3p, has-miR-940, has-miR-4284, and has-miR-4281 were 5 downregulated miRNAs in this network. Furthermore, the lncRNA-miRNA-mRNA interactions such as KCNQ1OT1-has-miR-1202-ETS1 were revealed in the present ceRNA network. Key DEMs such as miR-33b-3p, miR-940, and miR-1202 may be involved in OA. miR-1202 may regulate OA development via histone acetyltransferase pathway binding function and cellular senescence pathway. Furthermore, KCNQ1OT1-has-miR-1202-ETS1 might be vital for the process of OA.

SUBMITTER: Liu C

PROVIDER: S-EPMC7137223 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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MicroRNA-1202 plays a vital role in osteoarthritis via KCNQ1OT1 has-miR-1202-ETS1 regulatory pathway.

Liu Changzeng C Gao Jianming J Su Guangyan G Xiang Yang Y Wan Le L

Journal of orthopaedic surgery and research 20200406 1

<h4>Background</h4>This study aimed to explore the molecular mechanism of osteoarthritis (OA) and provide information about new genes as potential targets for OA treatment.<h4>Methods</h4>Gene expression profile of GSE105027, including 12 OA serum samples (OA group) and 12 healthy serum samples (ctrl group), was downloaded. The differentially expressed miRNAs (DEMs) as well as miRNA-mRNAs interactions were investigated, followed by function and pathway investigation. Then the protein-protein int ...[more]

PMID: 32252801

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Project description:UnlabelledEnterovirus 71 (EV71), a member of Picornaviridae, is associated with severe central nervous system complications. In this study, we identified a cellular microRNA (miRNA), miR-197, whose expression was downregulated by viral infection in a time-dependent manner. In miR-197 mimic-transfected cells, EV71 replication was inhibited, whereas the internal ribosome entry site (IRES) activity was decreased in EV71 strains with or without predicted miR-197 target sites, indicating that miR-197 targets host proteins to modulate viral replication. We thus used a quantitative proteomics approach, aided by the TargetScan algorithm, to identify putative target genes of miR-197. Among them, RAN was selected and validated as a genuine target in a 3' untranslated region (UTR) reporter assay. Reduced production of RAN by RNA interference markedly reduced the synthesis of EV71-encoded viral proteins and virus titers. Furthermore, reintroduction of nondegradable RAN into these knockdown cells rescued viral protein synthesis. miR-197 levels were modulated by EV71 to maintain RAN mRNA translatability at late times postinfection since we demonstrated that cap-independent translation exerted by its intrinsic IRES activity was occurring at times when translation attenuation was induced by EV71. EV71-induced downregulation of miR-197 expression increased the expression of RAN, which supported the nuclear transport of the essential viral proteins 3D/3CD and host protein hnRNP K for viral replication. Our data suggest that downregulation of cellular miRNAs may constitute a newly identified mechanism that sustains the expression of host proteins to facilitate viral replication.ImportanceEnterovirus 71 (EV71) is a picornavirus with a positive-sense single-stranded RNA that globally inhibits the cellular translational system, mainly by cleaving cellular eukaryotic translation initiation factor 4G (eIF4G) and poly(A)-binding protein (PABP), which inhibits the association of the ribosome with the host capped mRNA. We used a microRNA (miRNA) microarray chip to identify the host miRNA 197 (miR-197) that was downregulated by EV71. We also used quantitative mass spectrometry and a target site prediction tool to identify the miR-197 target genes. During viral infection, the expression of the target protein RAN was upregulated considerably, and there was a parallel downregulation of miR-197. The nuclear transport of viral 3D/3CD protein and of the host proteins involved in viral replication proceeded in an RAN-dependent manner. We have identified a new mechanism in picornavirus through which EV71-induced cellular miRNA downregulation can regulate host protein levels to facilitate viral replication.

Dataset Information

MicroRNA-1202 plays a vital role in osteoarthritis via KCNQ1OT1 has-miR-1202-ETS1 regulatory pathway.

Publications

MicroRNA-1202 plays a vital role in osteoarthritis via KCNQ1OT1 has-miR-1202-ETS1 regulatory pathway.

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