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

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.
Journal: 
Cell Death & Disease
Publication Date: 
27 Sep 2018
Citation: 
[DHA+18] Diener, C., Hart, M., Alansary, D., Poth, V., Walch-Rückheim, B., Menegatti, J., Grässer, F., Fehlmann, T., Rheinheimer, S., Niemeyer, B.A., Lenhof, H.-P., Keller, A., Meese, E. Modulation of intracellular calcium signaling by microRNA-34a-5p. Cell death & disease 9 (10), 1008, 2018. DOI: 10.1038/s41419-018-1050-7.
Researchers: