MicroRNA-223 promotes mast cell apoptosis by targeting the insulin-like growth factor 1 receptor

Abstract

The present study aimed to examine the functional role of miR-223 in the regulation of mast cell apoptosis. Overexpressed miR-223 in mast cells transfected by Lipofectamine 2000 was used as a model, and miR-223 was found to promote mast cell apoptosis. To investigate the underlying mechanisms involved, the potential and putative target molecules of miR-223 were detected by bioinformatical analysis using predictive software, and western blotting. Insulin-like growth factor-1 receptor (IGF-1R) was found to be the functional target of miR-223 in the promotion of cell apoptosis. The downstream PI3K/protein kinase B (Akt) signaling pathway was also inhibited, and signaling was mediated by IGF-1R. Furthermore, the relative luciferase activity of the reporter containing the 3′-untranslated region (3′-UTR) of IGF-1R was significantly suppressed, while suppression of miR-223-inhibited IGF-1R protein expression was also observed. In conclusion, the results suggest that IGF-1R is the functional target for miR-223 promotion of cell apoptosis, and its downstream PI3K/Akt signaling pathway was suppressed by miR-223 through targeting of IGF-1R.

MicroRNA‑126 accelerates IgE‑mediated mast cell degranulation associated with the PI3K/Akt signaling pathway by promoting Ca2+ influx

“…As the PI3K conformation changes, Ser473 and Thr308 phosphorylation is required for Akt activation (21). A number of previous studies have demonstrated that the PI3K/Akt signaling pathway participated in the regulation of miRNAs on MC degranulation (22)(23)(24). miR-155 controlled MC activation by modulating the PI3Kγ signaling pathway and anaphylaxis in mice with cutaneous anaphylaxis (22).…”

“…miR-155 controlled MC activation by modulating the PI3Kγ signaling pathway and anaphylaxis in mice with cutaneous anaphylaxis (22). Downregulation of miR-223 promoted MC degranulation via the PI3K/Akt pathway by targeting insulin-like growth factor 1 receptor (23). Lentiviral short hairpin RNA against KCa3.1 inhibited the allergic response in allergic rhinitis and suppressed MCs activity via the PI3K/AKT signaling pathway (24).…”

Propofol attenuates mast cell degranulation via inhibiting the miR‑221/PI3K/Akt/Ca2+ pathway

“…The effect of PI3K/Akt signaling in mast cells has previously been investigated (22,23), as has the association between miR expression and PI3K/Akt signaling in mast cell degranulation (24,25). Although miR-223 expression was upregulated in IgE-mediated mast cells, miR-223 downregulation was demonstrated to promote mast cell degranulation and apoptosis via the PI3K/Akt pathway by targeting insulin-like growth factor 1 receptor in mast cells (25,26). Helicobacter pylori neutrophil-activating protein induced the release of histamine and interleukin-6 in human mast cell line-1 via the G protein-mediated mitogen-activated protein kinase (MAPK) and PI3K/Akt pathways (27).…”

miRNA‐15a, miRNA‐16, miRNA‐126, miRNA‐146a, and miRNA‐223 expressions in autologous hematopoietic stem cell transplantation and their impact on engraftment

“…35 miRNA-223 is significantly involved in neoplastic cell development by targeting oncogene BCL-2 and the insulin growth factor 1 receptor (IGF-1R). 40 To the best of our knowledge, the complex network of miRNAs that play major roles in hematopoietic niche microenvironment homeostasis has not been assessed so far in the context of HSC transplantation. The aim of this study was to evaluate the miRNAs involved in angiogenesis, hematopoiesis, and homing of HSC in autologous transplantation setting.…”

“…In hematological malignancies, miRNA‐223 in bone marrow seems to be a tumor‐suppressive molecule . miRNA‐223 is significantly involved in neoplastic cell development by targeting oncogene BCL‐2 and the insulin growth factor 1 receptor (IGF‐1R) …”