Modulation of intracellular calcium signaling by microRNA-34a-5p

Modulation of intracellular calcium signaling by microRNA-34a-5p. Diener, C., Hart, M., Alansary, D., Poth, V., Walch-Rückheim, B., Menegatti, J., Grässer, F., Fehlmann, T., Rheinheimer, S., Niemeyer, B. A, Lenhof, H., Keller, A., & Meese, E. Cell death & disease, 9:1008, Nature Publishing Group, September, 2018.
doi abstract bibtex

Adjusting intracellular calcium signaling is an important feature in the regulation of immune cell function and survival. Here we show that miR-34a-5p, a small non-coding RNA that is deregulated in many common diseases, is a regulator of store-operated Ca2+ entry (SOCE) and calcineurin signaling. Upon miR-34a-5p overexpression, we observed both a decreased depletion of ER calcium content and a decreased Ca2+ influx through Ca2+ release-activated Ca2+ channels. Based on an in silico target prediction we identified multiple miR-34a-5p target genes within both pathways that are implicated in the balance between T-cell activation and apoptosis including ITPR2, CAMLG, STIM1, ORAI3, RCAN1, PPP3R1, and NFATC4. Functional analysis revealed a decrease in Ca2+ activated calcineurin pathway activity measured by a reduced IL-2 secretion due to miR-34a-5p overexpression. Impacting SOCE and/or downstream calcineurin/NFAT signaling by miR-34a-5p offers a possible future approach to manipulate immune cells for clinical interventions.

@Article{Diener2018,
  author       = {Caroline Diener and Martin Hart and Dalia Alansary and Vanessa Poth and Barbara Walch-Rückheim and Jennifer Menegatti and Friedrich Grässer and Tobias Fehlmann and Stefanie Rheinheimer and Barbara A Niemeyer and Hans-Peter Lenhof and Andreas Keller and Eckart Meese},
  title        = {Modulation of intracellular calcium signaling by microRNA-34a-5p},
  journal      = {Cell death & disease},
  year         = {2018},
  volume       = {9},
  pages        = {1008},
  month        = sep,
  issn         = {1008},
  abstract     = {Adjusting intracellular calcium signaling is an important feature in the regulation of immune cell function and survival. Here we show that miR-34a-5p, a small non-coding RNA that is deregulated in many common diseases, is a regulator of store-operated Ca2+ entry (SOCE) and calcineurin signaling. Upon miR-34a-5p overexpression, we observed both a decreased depletion of ER calcium content and a decreased Ca2+ influx through Ca2+ release-activated Ca2+ channels. Based on an in silico target prediction we identified multiple miR-34a-5p target genes within both pathways that are implicated in the balance between T-cell activation and apoptosis including ITPR2, CAMLG, STIM1, ORAI3, RCAN1, PPP3R1, and NFATC4. Functional analysis revealed a decrease in Ca2+ activated calcineurin pathway activity measured by a reduced IL-2 secretion due to miR-34a-5p overexpression. Impacting SOCE and/or downstream calcineurin/NFAT signaling by miR-34a-5p offers a possible future approach to manipulate immune cells for clinical interventions.},
  doi          = {10.1038/s41419-018-1050-7},
  issn-linking = {1008},
  issue        = {10},
  pii          = {10.1038/s41419-018-1050-7},
  publisher    = {Nature Publishing Group},
}

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