Aberrant Expression of miR-25-3p/EZH2 Is Involved in T Cell Activation in Aplastic Anemia.

This research aims to investigate how aberrantly expressed miR-25-3p and EZH2 regulate T cell activation in aplastic anemia (AA) patients and to explore the underlying mechanisms. The study enrolled 26 severe AA (SAA) patients and 22 healthy subjects. Quantitative reverse transcription polymerase chain reaction was used to detect the miR-25-3p, EZH2 and CD69 expression. After establishing an AA mouse model, cell viability, proteins expression levels and cytokines levels were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Western blot analysis, and enzyme-linked immunosorbent assay. A luciferase reporter assay was performed to verify the interaction between miR-25-3p and EZH2. Serum miR-25-3p expression was decreased in SAA patients (P < 0.001). Overexpression of miR-25-3p reduced cell viability and decreased CD69, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) levels; conversely, inhibition of miR-25-3p exerted the opposite effect (P < 0.001). EZH2 was a downstream target gene of miR-25-3p. Overexpression of EZH2 partially reversed the decrease in cell viability and the inhibition of CD69, IFN-γ and TNF-α levels caused by miR-25-3p upregulation (P < 0.01). MiR-25-3p was downregulated in SAA patients and regulated CD4+ T cell activation and proliferation by targeting EZH2. These findings provide novel insights into potential therapeutic targets for AA.