MiR-34a: a new player in the regulation of T cell function by modulation of NF-?B signaling.

ABSTRACT: NF-?B functions as modulator of T cell receptor-mediated signaling and transcriptional regulator of miR-34a. Our in silico analysis revealed that miR-34a impacts the NF-?B signalosome with miR-34a binding sites in 14 key members of the NF-?B signaling pathway. Functional analysis identified five target genes of miR-34a including PLCG1, CD3E, PIK3CB, TAB2, and NF?BIA. Overexpression of miR-34a in CD4+ and CD8+ T cells led to a significant decrease of NF?BIA as the most downstream cytoplasmic NF-?B member, a reduced cell surface abundance of TCRA and CD3E, and to a reduction of T cell killing capacity. Inhibition of miR-34a caused an increase of NF?BIA, TCRA, and CD3E. Notably, activation of CD4+ and CD8+ T cells entrails a gradual increase of miR-34a. Our results lend further support to a model with miR-34a as a central NF-?B regulator in T cells.

SUBMITTER: Hart M 

PROVIDER: S-EPMC6362007 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other