biostudies-literatureHart MDeutsche ForschungsgemeinschaftEC | Seventh Framework ProgrammeMichael J. Fox Foundation for Parkinson's Research46https://www.ebi.ac.uk/biostudies/studies/S-EPMC6362007biostudies-literatureUnknown10(2)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.Cell death & diseasemiR-34a: a new player in the regulation of T cell function by modulation of NF-κB signaling.PMC6362007SFB894Hart MWalch-Ruckheim BTanzer TKeller AGlombitza BFriedmann KSRheinheimer SLenhof HPHoth MMeese ESester MSchwarz ECfalsemiR-34a: a new player in the regulation of T cell function by modulation of NF-κB signaling.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.2019-01-01T00:00:00Z2019 Jan2025-04-25T17:25:44.971Z2019-03-26T22:50:47ZS-EPMC63620073071847510.1038/s41419-018-1295-1