CeRNA network identified hsa-miR-17-5p, hsa-miR-106a-5p and hsa-miR-2355-5p as potential diagnostic biomarkers for tuberculosis.

This study aims to analyze the regulatory non-coding RNAs in the pathological process of tuberculosis (TB), and identify novel diagnostic biomarkers. A longitudinal study was conducted in 5 newly diagnosed pulmonary tuberculosis patients, peripheral blood samples were collected before and after anti-TB treatment for 6 months, separately. After whole transcriptome sequencing, the differentially expressed RNAs (DE RNAs) were filtrated with |log2 (fold change) | > log2(1.5) and P value < .05 as screening criteria. Then functional annotation was actualized by gene ontology enrichment analysis, and enrichment pathway analysis was conducted by Kyoto Encyclopedia of Genes and Genomes database. And finally, the competitive endogenous RNA (ceRNA) regulatory network was established according to the interaction of ceRNA pairs and miRNA-mRNA pairs. Five young women were recruited and completed this study. Based on the differential expression analysis, a total of 1469 mRNAs, 996 long non-coding RNAs, 468 circular RNAs, and 86 miRNAs were filtrated as DE RNAs. Functional annotation demonstrated that those DE-mRNAs were strongly involved in the cellular process (n = 624), metabolic process (n = 513), single-organism process (n = 505), cell (n = 651), cell part (n = 650), organelle (n = 569), and binding (n = 629). Enrichment pathway analysis revealed that the differentially expressed genes were mainly enriched in HTLV-l infection, T cell receptor signaling pathway, glycosaminoglycan biosynthesis-heparan sulfate/heparin, and Hippo signaling pathway. CeRNA networks revealed that hsa-miR-17-5p, hsa-miR-106a-5p and hsa-miR-2355-5p might be regarded as potential diagnostic biomarkers for TB. Immunomodulation-related genes are differentially expressed in TB patients, and hsa-miR-106a-5p, hsa-miR-17-5p, hsa-miR-2355-5p might serve as potential diagnostic biomarkers.

A functional polymorphism at the miR­491­5p binding site in the 3'­untranslated region of the MMP­9 gene increases the risk of developing ventilator­associated pneumonia.

Matrix metalloproteinase (MMP)­9 is associated with the severity of ventilator­associated pneumonia (VAP), while an rs1056629 SNP located in the 3'­untranslated region (UTR) of MMP­9 affects the microRNA (miRNA/miR)­491­mediated regulation of MMP­9 expression. In the present study, the effect of rs1056629 on the development of VAP in patients with chronic obstructive pulmonary disease (COPD) was investigated. Patients with COPD were enrolled in the study and their genotypes of rs1056629 (CC, CA or AA) were determined. ELISA was used to analyze the levels of TNF­α and IL­6 in the monocytes of patients with COPD carrying differential genotypes of rs1056629. Reverse transcription­quantitative PCR was carried out to evaluate the expression of miR­491 and MMP­9 mRNA in the different groups of patients with COPD. Luciferase assay was used to confirm the inhibitory role of miR­491 in MMP­9 expression. Western blot analysis was carried out to assess the expression of MMP­9 protein in A549 and H1299 cells transfected with miR­491 mimics. The risk and severity of VAP were significantly elevated in patients with COPD carrying the CC and AC genotypes of rs1056629. Although there was no difference in the expression of miR­491 in patients carrying different genotypes of rs1056629, the expression levels of TNF­α, IL­6 and MMP­9 were increased in patients with COPD carrying the CC and AC genotypes of rs1056629. The results of luciferase assay revealed that miR­491 inhibited the expression of MMP­9 through direct binding to the 3'UTR of MMP­9. Transfection of miR­491 mimics into A549 and H1299 cells markedly suppressed the expression of MMP­9 in a concentration­dependent manner. On the whole, the findings of the present study confirm that the CC and AC genotypes of rs1056629 increase the risk of developing VAP in patients with COPD by increasing the expression of MMP­9.