The Expression And Bioinformatics Analysis Of MiR-17-92 Gene Cluster And Parts Of MiRNAs Transcribed From It In Interspinal Schwannoma

Background:Interspinal Schwannoma(IS),whose process of tumorigenesis is unclear,is an intraspinal extramedullary benign tumor.Increasing evidences show miRNAs regulated by upstream transcription factors(TFs)regulate the expression of genes coding proteins via binding mRNAs transcribed from their downstream target genes.Hsa-miR-17-92 gene cluster is polycistronic miRNA gene cluster,which encodes miR-17,miR-18a,miR-19a,miR-19b,miR-20a and miR-92a,and participates in lots of biological processes.However,it is not clear that how the expression,effects and regulatory pathways related with this gene cluster in IS will be.Objective:In this study,we primarily investigated the expression of miR-17-92 gene cluster and seven miRNAs(miR-17-5p,miR-17-3p,miR-18a-5p,miR-19a-3p,miR-19b-3p,miR-20a-5p and miR-92a-3p)transcribed from it in specimens of IS and lower extremity nerve(LN),built TFs-miRNA-mRNAs networks of miR-17-5p,miR-18a-5p,miR-20a-5p and miR-92a-3p,and analyzed protein-protein interactions(PPIs)Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway of their downstream target genes predicated.Methods:Specimens of 20 cases of IS and 10 cases of LN were collected under aseptic conditions.The expression of miR-17-92 gene cluster and seven miRNAs(miR-17-5p,miR-17-3p,miR-18a-5p,miR-19a-3p,miR-19b-3p,miR-20a-5p and miR-92a-3p)transcribed from it were tested by RT-qPCR.miRbase,PROMO and Targetscan were employed to predict upstream TFs and downstream target genes of miR-17-5p,miR-18a-5p,miR-20a-5p and miR-92a-3p.PPIs were analyzed by STRING v10 and TFs-miRNA-mRNAs networks were built via Cytoscape.Analysis of GO and KEGG pathway of target genes were done via KOBAS3.0 and clusterProfiler R software.Results:Compared to LN,the expression of miR-17-92 gene cluster and remained six miRNAs is lower(P<0.05)apart from miR-17-3p(P=8.664E-02).This change is especially notable in miR-18a-5p and miR-20a-3p.A large of TFs-miRNAs-mRNAs networks were built.Target genes predicted were enriched in positive regulation of catabolic process of nitrogen compound in neurons and cynapses and enriched in spheres of protein serine/threonine kinase activity and transcription factor activity through analysis of GO.Analysis of KEGG pathway elucidated many target genes predicted involved in the regulation of axon guidance(AG).Conclusion:According to the results above,some conclusions can be drawn as follows:1.The mechanism that miR-17-92 gene cluster participates in tumorigenesis of IS may be achieved by miR-17-5p,miR-18a-5p,miR-19a-3p,miR-19b-3p,miR-20a-5p and miR-92a-3p transcribed from it.2.MiR-17-3p may not involve in tumorigenesis of IS,or it is not an important factor in tumorigenesis of IS.3.MiR-17-3p.miR-18a-5p.miR-20a-5p and miR-92a-3p and TFs-miRNA-mRNAs networks based them participate in AG via several signaling pathways including protein serine/threonine kinase pathway and may be potential targets and vital research fields for diagnosis and treatment of IS.