Construction of a lncRNA–miRNA–mRNA Network to Determine the Key Regulators of the Th1/Th2 Imbalance in Multiple Sclerosis

Abstract

<b>Aim:</b> 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. <b>Methods:</b> A combination of bioinformatics analysis and molecular evaluations was utilized to identify master hub genes. <b>Results:</b> 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. <i>NEAT1</i> and <i>MALAT1</i> were found as differentially expressed lncRNAs using Gene Expression Omnibus (GSE21942). Quantitative real-time PCR results demonstrate dysregulation in the <i>RUNX3</i> (a regulator of Th1/Th2 balance), <i>GATA3</i> and <i>TBX21</i>, as well as miR-544a and miR-210-3p (which directly target <i>RUNX3</i>). ELISA also confirmed an imbalance in IFN-γ (Th1)/IL-4 (Th2) in MS patients. <b>Conclusion:</b> Our findings introduce novel biomarkers leading to Th1/Th2 imbalance in MS.