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

Abstract: 
NF-κB 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-κB signalosome with miR-34a binding sites in 14 key members of the NF-κB signaling pathway. Functional analysis identified five target genes of miR-34a including PLCG1, CD3E, PIK3CB, TAB2, and NFΚBIA. Overexpression of miR-34a in CD4+ and CD8+ T cells led to a significant decrease of NFΚBIA as the most downstream cytoplasmic NF-κB 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 NFΚBIA, 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-κB regulator in T cells.
Journal: 
Cell Death Disease
Publication Date: 
18 Jan 2019
Citation: 
[HWF+19] Hart, M., Walch-Rückheim, B., Friedmann, K.S., Rheinheimer, S., Tänzer, T., Glombitza, B., Sester, M., Lenhof, H.-P., Hoth, M., Schwarz, E.C., Keller, A., Meese, E. miR-34a: a new player in the regulation of T cell function by modulation of NF-κB signaling. Cell death & disease 10 (2), 46, 2019. DOI: 10.1038/s41419-018-1295-1.
Researchers: