Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis

Abstract

Myasthenia gravis (MG) is a neuromuscular autoimmune disorder resulting from autoantibodies attacking components of the neuromuscular junction. Recent studies have implicated the aberrant expression of microRNAs (miRNAs) in the pathogenesis of MG; however, the underlying mechanisms remain largely unknown. This study aimed to identify key genes regulated by miRNAs in MG. Six dysregulated pathways were identified through differentially expressed miRNAs and mRNAs in MG, and significant crosstalk was detected between five of these. Notably, crosstalk between the “synaptic long-term potentiation” pathway and four others was mediated by five genes involved in the MAPK signaling pathway. Furthermore, 14 key genes regulated by miRNAs were detected, of which six—MAPK1, RAF1, PGF, PDGFRA, EP300, and PPP1CC—mediated interactions between the dysregulated pathways. MAPK1 and RAF1 were responsible for most of this crosstalk (80%), likely reflecting their central roles in MG pathogenesis. In addition, most key genes were enriched in immune-related local areas that were strongly disordered in MG. These results provide new insight into the pathogenesis of MG and offer new potential targets for therapeutic intervention.

Plasma exosomal miR‐106a‐5p expression in myasthenia gravis

“…Moreover, exosomal miR‐106a‐5p expression was shown to be negatively correlated with patient QMGS, indicating its association with MG clinical typing and severity. Interestingly, one of the dysregulated miRNAs by deep‐sequencing in the present study, miR‐106a‐5p has been previously shown to be associated with the pathogenesis of many cancers, including melanoma, colorectal and gastric cancer, MG, and esophageal squamous‐cell carcinoma . Similarly, miR‐106a‐5p dysregulation has been reported in T‐cells of patients with immune diseases, and may inhibit the proliferation, migration, and invasion of carcinoma cells by modulating various mRNA targets .…”

“…[27][28][29][30] Similarly, miR-106a-5p dysregulation has been reported in T-cells of patients with immune diseases, and may inhibit the proliferation, migration, and invasion of carcinoma cells by modulating various mRNA targets. 24,31 Notably, CD4+ T and Th17 cells are known to mediate thymic changes that are associated with MG pathogenesis, 32 and it has been suggested that miR-106a-5p may suppress the differentiation of Th17 cells and downregulate the production of CD4+ T cells during the relapse phase of multiple sclerosis and in MG. 24,25 The above reasons explain why miR-106a-5p was chosen for further verification by RT-PCR.…”

Plasma MicroRNA Expression Profiles in Psoriasis

“…A P value < 0.05 was considered to have a significant difference. MicroRNA target genes were predicted using the following miRNA target prediction tools: miRanda (August 2010 release) [31] and TargetScan (http://www.targetscan.org/ vert_71/) [32]. Only genes predicted by both databases were chosen as conjectural miRNA targets for pathway analysis.…”

Integrative Analysis with Monte Carlo Cross-Validation Reveals miRNAs Regulating Pathways Cross-Talk in Aggressive Breast Cancer

“…To our knowledge, there are few studies that examine the role of miRNAs for cross-talked pathway able to correctly discriminate normal versus BC samples. Recently, in myasthenia gravis Cao et al [ 26 ] calculated the cross-talk between pathways, identified by pathway-enriched analysis based on a cumulative hypergeometric distribution. They obtained key genes regulated by miRNAs, and these miRNAs were found to mediate cross-talk.…”