Dysregulation of microRNAs regulating survivin in CD4+ T cells in multiple sclerosis

Impaired elimination mechanisms of the autoreactive lymphocytes, like T lymphocytes, via apoptosis may be the cause of continues inflammatory state in multiple sclerosis (MS). BIRC5 gene codify for the survivin, which participates in the modulation of apoptosis and cell survival. The objective of this study was investigation of the role of important confirmed miRNAs, including miR-335, miR-485, miR-542, and miR-708, in the regulation of survivin mRNA in the CD4+ T cells of MS cases.

In this study, 50 RRMS patients as well as 50 healthy matched controls were recruited. The peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples and CD4+ T cells were prepared. After that, RNA was extracted, cDNA was synthesized, and the expression levels of miR-335, miR-485, miR-542, and miR-708 were measured using Real-time PCR. Moreover, the mRNA expression of survivin was detected. Serum level of survivin was detected using ELISA.

The mRNA of survivin was 2-folds upregulated in the CD4+ T cells from MS patients in comparison to the healthy controls (P = 0.0053). Serum level of survivin was higher in patients than controls. There was statistically significant downregulation of miR-485 (P = 0.001) and miR-708 (P = 0.011) in CD4+ T cells of patients compared with controls. The miR-485 downregulation had statistically significant correlation with the mRNA expression and serum level of survivin.

miRNAs play a role in the regulation of survivin, and therefore apoptosis of CD4+ T cells, and hence are probably participating in a persistent inflammatory condition in MS patients.