Upregulation of Cd4+ T-Cell Derived Mir-223 in the Relapsing Phase of Multiple Sclerosis Patients



Hosseini A¹ ; Ghaedi K^{1, 2} ; Tanhaei S² ; Ganjalikhanihakemi M³ ; Teimuri S¹ ; Etemadifar M⁴ ; Esfahani MHN² Show Affiliations
Source: Cell Journal Published:2016

Abstract

Objective: MicroRNAs (miRNA) are a class of non-coding RNAs which play key roles in post-transcriptional gene regulation. Previous studies indicate that miRNAs are dysregulated in patients with multiple sclerosis (MS). Th17 and regulatory T (Treg) cells are two subsets of CD4+ T-cells which have critical functions in the onset and progression of MS. The current study seeks to distinguish?uctuations in expression of CD4+ T-cell derived miR-223 during the relapsing-remitting (RR) phase of MS (RR-MS), as well as the expressions of Th17 and Treg cell markers. Materials and Methods: This experimental study used real-time quantitative polymerase chain reaction (qRT-PCR) to evaluate CD4+ T cell derived miR-223 expression patterns in patients that experienced either of the RR-MS phases (n=40) compared to healthy controls (n=12), along with RNA markers for Th17 and Treg cells. We conducted?ow cytometry analyses of forkhead box P3 (FOXP3) and RAR-related orphan receptor?t (ROR?t) in CD4+ T-cells. Putative and validated targets of miR-223 were investigated in the miRWalk and miRTarBase databases, respectively. Results: miR-223 signifcantly upregulated in CD4+ T-cells during the relapsing phase of RR-MS compared to the remitting phase (P=0.000) and healthy individuals (P=0.036). Expression of ROR?t, a master transcription factor of Th17, upregulated in the relapsing phase, whereas FOXP3 upregulated in the remitting phase. Additionally, potential targets of miR-223, STAT1, FORKHEAD BOX O (FOXO1) and FOXO3 were predicted by in silico studies. Conclusion: miR-223 may have a potential role in MS progression. Therefore, suppression of miR-223 can be proposed as an appropriate approach to control progression of the relapsing phase of MS.