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

miR-34a: a new player in the regulation of T cell function by modulation of NF-κB signaling. Hart, M., Walch-Rückheim, B., Friedmann, K. S, Rheinheimer, S., Tänzer, T., Glombitza, B., Sester, M., Lenhof, H., Hoth, M., Schwarz, E. C, Keller, A., & Meese, E. Cell death & disease, 10:46, Nature Publishing Group, January, 2019.
doi abstract bibtex

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.

@Article{Hart2019,
  author       = {Martin Hart and Barbara Walch-Rückheim and Kim S Friedmann and Stefanie Rheinheimer and Tanja Tänzer and Birgit Glombitza and Martina Sester and Hans-Peter Lenhof and Markus Hoth and Eva C Schwarz and Andreas Keller and Eckart Meese},
  title        = {miR-34a: a new player in the regulation of T cell function by modulation of NF-κB signaling},
  journal      = {Cell death & disease},
  publisher    = {Nature Publishing Group},
  year         = {2019},
  volume       = {10},
  issue        = {2},
  pages        = {46},
  issn         = {46},
  issn-linking = {46},
  month        = jan,
  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.},
  doi          = {10.1038/s41419-018-1295-1},
  pii          = {10.1038/s41419-018-1295-1},
}

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