Paper Information

Journal:   CELL JOURNAL (YAKHTEH)   FALL 2016 , Volume 18 , Number 3 (71); Page(s) 371 To 380.
 
Paper: 

UPREGULATION OF CD4+T-CELL DERIVED MIR-223 IN THE RELAPSING PHASE OF MULTIPLE SCLEROSIS PATIENTS

 
 
Author(s):  HOSSEINI AREF, GHAEDI KAMRAN*, TANHAEI SOMAYEH, GANJALIKHANI HAKEMI MAZDAK, TEIMURI SHOHREH, ETEMADIFAR MASOUD, NASRESFAHANI MOHAMMAD HOSSEIN*
 
* DEPARTMENT OF CELLULAR BIOTECHNOLOGY, CELL SCIENCE RESEARCH CENTER, ROYAN INSTITUTE FOR BIOTECHNOLOGY, ISFAHAN, IRAN
 
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 fluctuations 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 flow 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 significantly 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 ofROR?t, a master transcription factor of Th17, upregulated in the relapsing phase, whereasFOXP3 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.

 
Keyword(s): CD4+T-CELL, MICRORNAS, MIR-223, MULTIPLE SCLEROSIS, TH17
 
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