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Modulation of intracellular calcium signaling by microRNA-34a-5p.
- Source :
-
Cell death & disease [Cell Death Dis] 2018 Sep 27; Vol. 9 (10), pp. 1008. Date of Electronic Publication: 2018 Sep 27. - Publication Year :
- 2018
-
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 Ca <superscript>2+</superscript> entry (SOCE) and calcineurin signaling. Upon miR-34a-5p overexpression, we observed both a decreased depletion of ER calcium content and a decreased Ca <superscript>2+</superscript> influx through Ca <superscript>2+</superscript> release-activated Ca <superscript>2+</superscript> 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 <superscript>2+</superscript> 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.
- Subjects :
- Apoptosis physiology
Calcineurin metabolism
Calcium Channels metabolism
Cell Line
Cell Line, Tumor
HEK293 Cells
Humans
Interleukin-2 metabolism
Jurkat Cells
Lymphocyte Activation physiology
NFATC Transcription Factors metabolism
Signal Transduction physiology
T-Lymphocytes metabolism
Calcium metabolism
Calcium Signaling genetics
MicroRNAs metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 9
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 30262862
- Full Text :
- https://doi.org/10.1038/s41419-018-1050-7