Fingolimod treatment induces expression of FENDRR lncRNA

Introduction: Fingolimod has gotten the FDA approval for Multiple Sclerosis (MS) treatment due to its capacity in trapping the lymphocytes at lymph nodes and decline the disease progression rate. For activation, Fingolimod would be transported actively to the cytosol and phosphorylated to play the role of sphingosine phosphate 1 (S1P) in triggering the downstream signaling pathways of S1PR1-5. In this study, we focused on the signaling pathways located downstream of S1PRs to find the possible targets of Fingolimod which could be involved in the drug’s action mechanism. We specifically considered lncRNAs altering the chromatin structure by binding to chromatin remodeler complexes. Methods: To find the possible target of Fingolimod, we analyzed the promoters of chromatin remodeler lncRNAs by JASPAR database to find the transcription factors binding sites for those factors located downstream of the S1PRs signaling pathway. Jurkat cell line was treated by 10nM and 100nM Fingolimod concentration in 24 and 48 hours and qRT-PCR was performed on cDNA samples. Results: Several lncRNAs including HOTAIR, ANRIL, and FENDRR were chosen by bioinformatics analysis and among them, FENDRR was dramatically overexpressed in response to Fingolimod treatments in a dose and time-dependent manner. Conclusion: Fingolimod could alter the chromatin structures by influences the expression of FENDRR and may play some aspects of its role in this way.

Keywords:

Fingolimod , FENDRR , lncRNA , S1P