Potential role of miR-425, miR-155 and miR-33 in Streptococcus pneumoniae pneumonia by using bioinformatics analysis and experimental validation.

Abstract

Streptococcus pneumoniae (S. pneumoniae) pneumonia is the most common cause of community-acquired pneumonia (CAP). Previous studies have suggested the diagnostic potential of microRNAs (miRNAs) in infectious diseases. In the present study, we aimed to evaluate the potential role of miRNAs in S. pneumoniae pneumonia by using bioinformatics analysis and experimental validation. Gene Expression Omnibus (GEO) datasets including GSE97922 and GSE83615 were analyzed for identifying the differentially expressed miRNAs; the miRNA-target genes network was constructed by using miRNet and the targeted genes were subject to Gene Ontology enrichment, Kyoto Encyclopedia of Genes and Genomes and REACTOME pathway analysis; the miRNA and mRNA expression levels were determined by quantitative real-time PCR; protein concentrations were determined by enzyme-linked immunosorbent assay. Our results showed that miR-425, miR-155 and miR-33 were up-regulated in the serum from CAP patients when compared to healthy controls; whereas there was no significant difference in serum miR-222, miR-149, miR-186 and miR-132 expression levels between healthy controls and CAP patients. In vitro functional studies showed that lipopolysaccharides (LPS) induced the up-regulation of miR-425, miR-155 and miR-33 in RAW264.7 cells, and miR-425, miR-155 and miR-33 inhibition attenuated LPS-induced inflammatory responses in RAW264.7 cells. In conclusion, our results showed that miR-425, miR-155 and miR-33 were up-regulated in the serum from CAP patients by using bioinformatics analysis and experimental validation; furthermore, miR-425, miR-155 and miR-33 inhibition attenuated LPS-induced inflammatory responses in RAW264.7 cells. Nevertheless, our studies are still at the preliminary stages, and the detailed roles of miR-425, miR-155 and miR-33 in S. pneumoniae pneumonia still require further investigation.