Fingolimod Regulates BDNF-AS and HOTAIR Expression in Multiple Sclerosis Patients

Abstract Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is expressed by neurons and glial cells in the central nervous system (CNS). In the CNS, BDNF is responsible for neuroprotection and neurogenesis. Recent studies showed that the Fingolimod, the first oral medicine for relapsing-remitting multiple sclerosis (RR-MS), induces BDNF expression. Besides, It is well demonstrated that long noncoding RNAs (lncRNAs) have a pivotal role in gene regulation. This study is mainly focused on how Fingolimod treatment plays role in BDNF regulation in coordination with lncRNAs. An in-silico study was performed to predict BDNF-regulatory candidate lncRNAs using online tools. Then, the expression of BDNF-related lncRNAs was analyzed in patients with relapsing-remitting multiple sclerosis (RRMS) at baseline and after three months of Fingolimod treatment. Based on in silico results, two lncRNAs with potential regulatory functions on the BDNF including, Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and HOX Transcript Antisense RNA (HOTAIR), and also natural antisense of BDNF were selected. Fingolimod treatment increased the expression of HOTAIR lncRNA; however, the BDNF antisense RNA (BDNF-AS) expression was reduced dramatically. Furthermore, the results indicate a positive correlation between HOTAIR and MALAT1 lncRNAs and BDNF. Also, after Fingolimod treatment, the patients’ EDSS scores were declined or remained unchanged, indicating disease hindrance by Fingolimod therapy. Altogether, fingolimod exerts protective roles in RRMS patients probably by the mediation of HOTIAR and BDNF-AS lncRNAs.