Identification and functional analysis of specific MS risk miRNAs and their target genes.

BACKGROUND: It has been widely acknowledged that abnormal expression of microRNAs (miRNAs) may lead to the occurrence and development of MS through regulating target genes. Currently, only few studies have comprehensively evaluated the function and relationship between MS-related miRNAs and their target genes. METHODS: Differentially expressed miRNAs in MS patients' serum and plasma were selected by reviewing numerous literatures manually. Then, thousands of target genes were screened by several online databases, of which 899 MS-related genes were further identified. Gene ontology, protein-protein interaction and KEGG pathway analysis were used to determine high-risk pathways and MS risk genes. Transcriptomic datasets from GEO was analyzed to evaluate these risk genes. RESULTS: 28 MS-related miRNAs were extracted. MiR-30e, miR-93, miR-155 were identified as the most crucial miRNAs through targeting hub genes: PIK3CA, PIK3R1, PIK3R2 and MAPK8. Seven immune pathways were screened out according to KEGG pathway analysis. Six transcriptomic datasets were used to evaluate results, and PIK3CA was differentially expressed in MS patients compared with healthy donors. CONCLUSIONS: According to our research, MS-related miRNAs and their target genes of MS were identified and comprehensively evaluated. This work may provide a new insight for discovering pathogenesis and possible biomarkers of MS in future studies.

Identifying characteristic miRNAs-genes and risk pathways of multiple sclerosis based on bioinformatics analysis.

Multiple sclerosis is a chronic autoimmune disorder of the central nervous system. In MS, the genetic susceptibility is high and currently there is no effective treatment. MicroRNA, a small non-coding RNA, plays a vital role in immune responses. Aberrant or dysfunctional miRNAs may cause several diseases, including MS, thus miRNAs and miRNA related genes may be therapeutic weapons against MS. Here, we identified 21 miRNAs in peripheral blood mono-nuclear cells from over 600 persons, including healthy controls. By using informatics databases, 1637 susceptibility genes were evaluated and Cytoscape was used to integrate and visualize the relation between the miRNA identified and susceptibility genes. By using the cluster Profile package, a total of 10 risk pathways were discovered. Top pathways included: hsa05200 (pathway in cancer), hsa04010 (MAPK signaling pathway), and hsa04060 (cytokine-cytokine receptor interaction). By using the STRING database, a protein-protein interaction network was conducted to identify highly susceptibility genes. Moreover, the GSE21942 dataset was used to indicate the gene expression profiles and to correct prediction results, thereby identifying the most pivotal genes. The MiRSystem database provided information on both pivotal miRNAs and genes. In conclusion, miR-199a and miR-142-3p may be crucial for MS by targeting pivotal susceptibility genes, in particular KRAS and IL7R.