Expression Profile Of Circular RNA In Multiple Sclerosis

Background & Objective: Multiple sclerosis is a central nervous system immunerelated disease that is still incurable at present.Its pathogenesis is very complicated and its treatment is limited.Circular RNA is a new member of the non-coding RNA family and was originally thought to be a byproduct of RNA aberrant splicing.In recent years it has been found that circular RNA is involved in the physiological and pathological processes of many organisms.However,the role and possible mechanisms of circular RNA in multiple sclerosis remain unclear.Therefore,we collected the peripheral blood mononuclear cells(PBMCs)from patients with multiple sclerosis,examined the expression profile of circular RNA,and analyzed the possible role of differential expression of circular RNA.Methods: We enrolled 12 patients with multiple sclerosis according to the McDonald diagnostic criteria for multiple sclerosis,and included 12 healthy controls matched with age and gender,and then randomly selected 5 patients and 5 corresponding healthy controls.The total RNA of peripheral blood mononuclear cells(PBMCs)was extracted and detected by circRNA Sequencing.After sequencing,the STAR software was used to compare with the reference genome.The DCC software detected and identified the circular RNA.After annotating the circular RNA with some database such as circBase,the differentially expressed circular RNAs were finally screened by the edgeR software.Next,we performed GO(Gene Ontology)functional analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway analysis on the host genes of the differentially expressed circular RNAs.Finally,we used Targetscan and Miranda software to predict the miRNA binding sites of significantly differentially expressed circular RNAs,and deduced the circular RNAs that might have the function of "miRNA sponge",and obtained the first 5 miRNAs with the strongest binding force with them.Results: In this experiment,we screened a total of 246 significantly differentially expressed circular RNAs,including 197 significantly up-regulated and 49 significantly down-regulated circular RNAs,which constitute a differential expression profile of circular RNA in multiple sclerosis.Then,through bioinformatics analysis,we found that the host genes of the differentially expressed circRNAs are mainly enriched in the cell cycle replication,apoptosis process,immune inflammatory response,secretion regulation of cytokines and chemokines,organization inflammation-related endothelial and stem cell differentiation,phagocytosis and energy metabolism,protein methylation modification and other inflammatory immune-related cellular functions.The KEGG signaling pathway is mainly enriched in mTOR signaling pathway,ubiquitin-mediated proteolysis,Notch signaling pathway,HIF-1 signaling pathway,phospholipase D signaling pathway,thyroid hormone signaling pathway,etc.These signaling pathways may be associated with multiple sclerosis.Based on the circRNA-miRNA interaction,we predicted the interaction of miRNA with 246 circular RNAs,and each circRNA predicted the top five miRNAs with the most likely effect.We have found that multiple miRNAs such as miR-96,miR-30 a,and miR-212 have been reported in previous studies to be associated with the pathogenesis of multiple sclerosis,and this time it was predicted that circular RNAs might interact with them,which provides more comprehensive information for the study of multiple sclerosis.Conclusion: There are a large number of circular RNAs in peripheral blood mononuclear cells(PBMCs)of patients with multiple sclerosis and healthy volunteers,and some of them are significantly differentially expressed.These circRNAs are likely to participate in the pathogenesis and disease progression of multiple sclerosis.Differentially expressed circular RNAs have been shown in bioinformatics analysis of GO and KEGG,participating in various biological processes involved in the pathogenesis of multiple sclerosis,such as immune inflammation and cytokine stimulation.And through the prediction of circRNA-miRNA interactions,it is found that there is a certain degree of regulatory relationship between them.Specific functional circular RNAs still require more experimental validation,and they may become new targets for multiple sclerosis treatment.