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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 Ca 2+  entry (SOCE) and calcineurin signaling. Upon miR-34a-5p overexpression, we observed both a decreased depletion of ER calcium content and a decreased Ca 2+  influx through Ca 2+  release-activated Ca 2+  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 Ca 2+  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.

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