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

Aim: The exact epigenetic mechanisms that determine the balance of T helper (Th)1 and Th2 cells 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 Gene Expression Omnibus (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-γ (Th1)/IL-4 (Th2) in MS patients. Conclusion: Our findings introduce novel biomarkers leading to Th1/Th2 imbalance in MS.