Identification of novel microRNA signatures linked to acquired aplastic anemia

• Published in: Haematologica (Roma) Vol. 100; no. 12; pp. 1534 - 1545
• Main Authors: Hosokawa, K., Muranski, P., Feng, X., Keyvanfar, K., Townsley, D. M., Dumitriu, B., Chen, J., Kajigaya, S., Taylor, J. G., Hourigan, C. S., Barrett, A. J., Young, N. S.
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.12.2015
• Subjects: Adolescent; Adult; Aged; Anemia, Aplastic - immunology; Anemia, Aplastic - pathology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Female; Gene Expression Profiling; Gene Expression Regulation - immunology; Humans; Lymphocyte Activation; Male; MicroRNAs - immunology; Middle Aged
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2015.126128

Emerging evidence indicates that microRNA control and modulate immunity. MicroRNA have not been investigated in acquired aplastic anemia, a T-cell-mediated immune disease. Analysis of 84 microRNA expression levels in CD4(+) and CD8(+) T cells of patients with aplastic anemia revealed concurrent down-regulation of miR-126-3p, miR-145-5p, miR-223-3p, and miR-199a-5p (>3-fold change, P<0.05) in both T-cell populations, which were unique in aplastic anemia compared to other hematologic disorders. MiR-126-3p and miR-223-3p were down-regulated in CD4(+) T effector memory cells, and miR-126-3p, miR-145-5p, and miR-223-3p were down-regulated in CD8(+) T effector memory and terminal effector cells. Successful immunosuppressive therapy was associated with restoration to normal expression levels of miR-126-3p, miR-145-5p, and miR-223-3p (>2-fold change, P<0.05). In CD4(+) and CD8(+) T cells in aplastic anemia patients, MYC and PIK3R2 were up-regulated and proved to be targets of miR-145-5p and miR-126-3p, respectively. MiR-126-3p and miR-145-5p knockdown promoted proliferation and increased interferon-γ and granzyme B production in both CD4(+) and CD8(+) T cells. Our work describes previously unknown regulatory roles of microRNA in T-cell activation in aplastic anemia, which may open a new perspective for development of effective therapy. Clinicaltrials.gov identifier: NCT 01623167.