Global pathway view analysis of microRNA clusters in myasthenia gravis

Abstract

The significant roles of microRNAs (miRNAs) in the pathogenesis of myasthenia gravis (MG) have been observed in numerous previous studies. The impact of miRNA clusters on immunity has been demonstrated in previous years; however, the regulation of miRNA clusters in MG remains to be elucidated. In the present study, 245 MG risk genes were collected and 99 MG risk pathways enriched by these genes were identified. A catalog of 126 MG risk miRNAs was then created; the MG risk miRNAs were located on each chromosome and a miRNA cluster was defined as a number of miRNAs with a relative distance of <6 kb on the same sub-band, same band, same region and same chromosome. Furthermore, enrichment analyses were performed using the target genes of the MG risk miRNA clusters, and a number of risk pathways of each miRNA clusters were identified. As a result, 15 significant miRNA clusters associated with MG were identified. Additionally, the most significant pathways of the miRNA clusters were identified to be enriched on chromosomes 9, 19 and 22, characterized by immunity, infection and carcinoma, suggesting that the mechanism of MG may be associated with certain abnormalities of miRNA clusters on chromosomes 9, 19 and 22. The present study provides novel insight into a global pathway view of miRNA clusters in the pathogenesis of MG.

Construction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis

“…4A,B, seven pathways (PI3K-Akt signalling pathway and pathways in cancer, hepatitis B, bladder cancer, colorectal cancer, pancreatic cancer and prostate cancer) and two gene functions (positive regulation of cell proliferation and cytoplasm) were collectively enriched in both gene and miRNA analyses. Among these coenriched pathways, five were associated with cancer, and one was associated with infectious diseases, which is in accordance with our previous findings [15][16][17] .…”

“…Although the present study has some similarities with our previous studies [15][16][17] , for example: (i) miRNA and gene sets of MG were re-updated based on the previous studies; (ii) the same method was used for functional enrichment analysis, and immune and cancerous pathways always represent the characteristics of MG; (iii) networks were built to screen out prominent molecules. However, there are still many differences and outstanding points in the current study: (i) TFs were first introduced to form FFLs with miRNAs and genes for MG; (ii) 21 drugs screened in the current study went through a strict criteria, and compared to the 13 drugs in the previous study 16 , only one drug (Bevacizumab) overlapped.…”

“…We obtained MG risk genes and microRNA data following previously described criteria [15][16][17] . MG risk genes were retrieved by searching the literature in the PubMed database (https ://www.ncbi.nlm.nih.gov/pubme d) published before October 1st, 2018, following the criteria we set: the gene was notably differentially expressed in more than five MG samples using dependable biological laboratory techniques and through several databases we mentioned previously [15][16][17] . In addition, the catalogue of MG risk genes was updated based on our previous research 17 , and the number of MG risk genes increased from 245 to 263 (Table S3), including 131 manually collected genes (Table S4) and 132 genes from databases.…”

“…MG risk genes were retrieved by searching the literature in the PubMed database (https ://www.ncbi.nlm.nih.gov/pubme d) published before October 1st, 2018, following the criteria we set: the gene was notably differentially expressed in more than five MG samples using dependable biological laboratory techniques and through several databases we mentioned previously [15][16][17] . In addition, the catalogue of MG risk genes was updated based on our previous research 17 , and the number of MG risk genes increased from 245 to 263 (Table S3), including 131 manually collected genes (Table S4) and 132 genes from databases. MicroRNAs involved in MG were also obtained through a comprehensive literature search published before October 1st, 2018 as well as through databases such as miR2Disease 38 (http://www.mir2d iseas e.org/), the Nervous System Disease NcRNAome Atlas database (NSDNA) 39 (http://www.bio-bigda ta.net/nsdna /), and the Human microRNA Disease Database (HMDD v3.0) 40 (http://www.cuila b.cn/hmdd).…”

Emerging Roles of Dysregulated MicroRNAs in Myasthenia Gravis

“…These genes function in cell proliferation, maturation, differentiation, apoptosis, and other life processes (e.g., immune regulation) (Carthew and Sontheimer, 2009). In recent years, studies have demonstrated that the pathogenesis of MG is associated with thymus abnormalities and multiple genetic and environmental factors; abnormal miRNA function may also be involved in the pathological process of MG (Bo et al, 2019). For example, miR-146 expression was significantly upregulated in MG patients and accompanied by high TLR4, CD40, and CD80 expression levels in AChR-specific B cells (Lu et al, 2013), miR-15a appeared to be involved in the regulation of inflammatory cytokine expression in MG patients (Liu et al, 2016) and miR-125a-5p in the thymus may negatively regulate Foxp expression, leading to an imbalance in autoimmune regulation and MG pathogenesis (Li et al, 2016).…”