Identification of novel microRNA signatures linked to acquired aplastic anemia

Kohei Hosokawa, Pawel Muranski, Xingmin Feng, Keyvan Keyvanfar, Danielle M. Townsley, Bogdan Dumitriu, Jichun Chen, Sachiko Kajigaya, James G. Taylor, Christopher S. Hourigan, A. John Barrett, Neal S. Young

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1534-1545
Number of pages12
JournalHaematologica
Volume100
Issue number12
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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