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

被引：29

作者：

Diener, Caroline ^{[1
]}

Hart, Martin ^{[1
]}

Alansary, Dalia ^{[2
]}

Poth, Vanessa ^{[2
]}

Walch-Rueckheim, Barbara ^{[3
,4
]}

Menegatti, Jennifer ^{[4
,5
]}

Graesser, Friedrich ^{[4
,5
]}

Fehlmann, Tobias ^{[6
]}

Rheinheimer, Stefanie ^{[1
]}

Niemeyer, Barbara A. ^{[2
]}

Lenhof, Hans-Peter ^{[7
]}

Keller, Andreas ^{[6
]}

Meese, Eckart ^{[1
]}

机构：

[1] Saarland Univ, Inst Human Genet, D-66421 Homburg, Germany

[2] Saarland Univ, Ctr Integrat Physiol & Mol Med, Sch Med, Mol Biophys, D-66421 Homburg, Germany

[3] Saarland Univ, Inst Virol, D-66421 Homburg, Germany

[4] Saarland Univ, Ctr Human & Mol Biol, D-66421 Homburg, Germany

[5] Saarland Univ, Inst Virol, Med Sch, D-66421 Homburg, Germany

[6] Saarland Univ, Chair Clin Bioinformat, D-66123 Saarbrucken, Germany

[7] Saarland Univ, Ctr Bioinformat, Saarland Informat Campus, D-66123 Saarbrucken, Germany

来源：

CELL DEATH & DISEASE | 2018年 / 9卷

关键词：

OPERATED CA2+ ENTRY; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; T-CELL-ACTIVATION; TRANSCRIPTION FACTORS; NF-AT; CYCLOPHILIN LIGAND; PERIPHERAL-BLOOD; EXPRESSION; CALCINEURIN; CHANNEL;

D O I：

10.1038/s41419-018-1050-7

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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, STIM7, ORAI3, RCAN1, PPP3R7, 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.

引用

页数：13

共 80 条

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