Construction of a lncRNA-miRNA-mRNA network to determine the key regulators of the Th1/Th2 imbalance in multiple sclerosis

Lay abstract Studies have shown that irregular control of noncoding RNAs (ncRNAs) in immune responses can lead to multiple sclerosis. T helper cells 1 and 2 (Th1/Th2) balance plays an important role in regulating inflammation in this disease. In this study, to investigate the molecular factors that may disrupt this balance, we investigated the role of ncRNAs. Our results suggest that miR-210-3p and miR-544a irregularities can disrupt the Th1/Th2 balances through targeting the RUNX3 gene, which consequently leads to IFN gamma/IL4 imbalance. It is also clarified that NEAT1 and MALAT1 long noncoding RNAs also have a role in this imbalance exerting their effect through miR-210-3p and miR-544a. This molecular pathway may provide significant information on multiple sclerosis disease development. Aim: The exact epigenetic mechanisms that determine the balance of T helper cells 1 and 2 (Th1/Th2) and autoimmune responses in multiple sclerosis (MS) remain unclear. We aim to clarify these. Methods: A combination of bioinformatics analysis and molecular evaluations was utilized to identify master hub genes. Results: A competitive endogenous RNA network containing six long noncoding RNAs (lncRNAs), 21 miRNAs and 86 mRNAs was provided through enrichment analysis and a protein-protein interaction network. NEAT1 and MALAT1 were found as differentially expressed lncRNAs using GEO (GSE21942). Quantitative real-time PCR results demonstrate dysregulation in the RUNX3 (a regulator of Th1/Th2 balance), GATA3 and TBX21, as well as miR-544a and miR-210-3p (which directly target RUNX3). ELISA also confirmed an imbalance in IFN-gamma (Th1)/IL-4 (Th2) in MS patients. Conclusion: Our findings introduce novel biomarkers leading to Th1/Th2 imbalance in MS.

Automated summary

Studies show that irregular control of immune response noncoding RNAs can lead to multiple sclerosis, with miR-210-3p and miR-544a irregularities disrupting the Th1/Th2 balance. Investigating ncRNAs and lncRNAs can offer novel biomarkers for understanding the development of multiple sclerosis.