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

• Published in: Cell death & disease 2019-01, Vol.10 (2), p.46-46, Article 46
• Main Authors: Hart, Martin, Walch-Rückheim, Barbara, Friedmann, Kim S., Rheinheimer, Stefanie, Tänzer, Tanja, Glombitza, Birgit, Sester, Martina, Lenhof, Hans-Peter, Hoth, Markus, Schwarz, Eva C., Keller, Andreas, Meese, Eckart
• Format: Article
• Language: English
• Subjects: 38/89; 42/34; 59/5; 631/250/2502/2055; 631/337/384/331; 631/80/86/388; 82/1; 82/29; 9/10; 96/106; 96/109; 96/31; 96/95; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - immunology; Antibodies; Binding sites; Biochemistry; Biomedical and Life Sciences; CD3 Complex - genetics; CD3 Complex - immunology; CD4 antigen; CD8 antigen; Cell activation; Cell Biology; Cell Culture; Cell surface; Class I Phosphatidylinositol 3-Kinases - genetics; Class I Phosphatidylinositol 3-Kinases - immunology; HEK293 Cells; Humans; Immunology; Jurkat Cells; Life Sciences; Lymphocytes; Lymphocytes T; MicroRNAs - genetics; MicroRNAs - immunology; NF-kappa B - genetics; NF-kappa B - immunology; NF-KappaB Inhibitor alpha - genetics; NF-KappaB Inhibitor alpha - immunology; NF-κB protein; Phospholipase C gamma - genetics; Phospholipase C gamma - immunology; Signal transduction; Signal Transduction - immunology; T cell receptors; T-Lymphocytes - immunology; Transcription; Transfection
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-1295-1

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.