MMiRNA-Viewer2, a bioinformatics tool for visualizing functional annotation for MiRNA and MRNA pairs in a network.

BACKGROUND: Although there are many studies on the characteristics of miRNA-mRNA interactions using miRNA and mRNA sequencing data, the complexity of the change of the correlation coefficients and expression values of the miRNA-mRNA pairs between tumor and normal samples is still not resolved, and this hinders the potential clinical applications. There is an urgent need to develop innovative methodologies and tools that can characterize and visualize functional consequences of cancer risk gene and miRNA pairs while analyzing the tumor and normal samples simultaneously. RESULTS: We developed an innovative bioinformatics tool for visualizing functional annotation of miRNA-mRNA pairs in a network, known as MMiRNA-Viewer2. The tool takes mRNA and miRNA interaction pairs and visualizes mRNA and miRNA regulation network. Moreover, our MMiRNA-Viewer2 web server integrates and displays the mRNA and miRNA gene annotation information, signaling cascade pathways and direct cancer association between miRNAs and mRNAs. Functional annotation and gene regulatory information can be directly retrieved from our web server, which can help users quickly identify significant interaction sub-network and report possible disease or cancer association. The tool can identify pivotal miRNAs or mRNAs that contribute to the complexity of cancer, while engaging modern next-generation sequencing technology to analyze the tumor and normal samples concurrently. We compared our tools with other visualization tools. CONCLUSION: Our MMiRNA-Viewer2 serves as a multitasking platform in which users can identify significant interaction clusters and retrieve functional and cancer-associated information for miRNA-mRNA pairs between tumor and normal samples. Our tool is applicable across a range of diseases and cancers and has advantages over existing tools.

The Role of Interferon Regulatory Factor 5 in Macrophage Inflammation During Osteoarthritis.

Mounting evidence suggests that aberrant immune responses are involved in the pathogenesis of osteoarthritis (OA). Synovial macrophages are likely involved. In this study, we sought to investigate the role of interferon regulatory factor 5 (IRF5). In vitro M1-polarized macrophages presented significantly higher IRF5 expression than M2-polarized macrophages. Interestingly, IRF5 expression was observed in macrophages from the synovial fluid of OA patients, and the level of IRF expression was positively correlated with disease severity, such that stage 4 OA synovial macrophages presented significantly higher levels of IRF5 than stage 2 and stage 3 OA synovial macrophages. Circulating monocytes from OA patients, on the other hand, expressed little IRF5. However, synovial fluid from OA patients could significantly upregulate IRF5 expression in circulating monocytes. Synovial macrophages also expressed significantly higher IL-12 than circulating monocytes, and circulating monocytes conditioned in OA synovial fluid demonstrated significantly higher IL-12 expression. Direct IRF5 transfection could increase IL-12 expression in circulating monocytes. Interestingly, IRF5-transfected monocytes promoted the expression of Th1-associated genes in naive CD4 T cells via an IL-12-dependent mechanism. Overall, our study demonstrated that IRF5 expression was associated with OA severity and could contribute to the activation of the M1-Th1 axis.