miR-34a: a new player in the regulation of T cell function by modulation of NF-κB signaling

NF-kappa 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-kappa B signalosome with miR-34a binding sites in 14 key members of the NF-kappa B signaling pathway. Functional analysis identified five target genes of miR-34a including PLCG1, CD3E, PIK3CB, TAB2, and NFKBIA. Overexpression of miR-34a in CD4(+) and CD8(+) T cells led to a significant decrease of NFKBIA as the most downstream cytoplasmic NF-kappa 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 NFKBIA, 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-kappa B regulator in T cells.