MicroRNA‑424 suppresses the proliferation of hemangioma‑derived endothelial cells by targeting VEGFR‑2

Fei,Zhewei; Qiu,Mingke; Qi,Xianqin; Dai,Yuxin; Wang,Shuqing; Quan,Zhiwei; Liu,Yingbin; Ou,Jingmin

doi:10.3892/mmr.2018.9409

MicroRNA‑424 suppresses the proliferation of hemangioma‑derived endothelial cells by targeting VEGFR‑2

Authors:
- Zhewei Fei
- Mingke Qiu
- Xianqin Qi
- Yuxin Dai
- Shuqing Wang
- Zhiwei Quan
- Yingbin Liu
- Jingmin Ou
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Affiliations: Department of General Surgery, Xinhua Hospital (Chong Ming) Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 202150, P.R. China, Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China
Published online on: August 21, 2018 https://doi.org/10.3892/mmr.2018.9409
Pages: 4065-4071

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Abstract

Hemangioma (HA) is a type of benign tumor common in infancy. The main feature of HA is the abnormal proliferation of vascular endothelial cells. To date, the pathogenesis of HA remains unclear. Fully understanding the process of HA tumorigenesis is essential for developing novel treatment for HAs. Dysregulation of microRNAs (miRNAs/miR) has been reported to be involved in the development of various diseases, including HA. In the present study, the expression of miR‑424 decreased in HA‑derived endothelial cells (HemECs). To elucidate the role of miR‑424 in HAs development, the present study overexpressed or inhibited miR‑424 in HemECs, revealing that miR‑424 overexpression significantly inhibited HemEC growth and promoted apoptosis, while the downregulation of miR‑424 promoted cell growth and inhibited cell apoptosis. To elucidate the underlying mechanism, bioinformatic analyses were performed, the result of which demonstrated that the 3'‑untranslated region of vascular endothelial growth factor receptor 2 (VEGFR‑2) may be a target of miR‑424. The result of a dual luciferase reporter assay confirmed that the expression of VEGFR‑2 was inhibited by miR‑424. In addition, it was revealed that the hyper‑phosphorylation of protein kinase B (AKT) and extracellular signal‑regulated kinase (ERK) in HemECs, and the restoration of miR‑424 markedly inhibited the activation of AKT and ERK. In conclusion, these results indicated that miR‑424 may target VEGFR‑2 and inhibit HemECs growth, and that low expression of miR‑424 in HemECs may lead to an increase in cell growth and a decrease in cell apoptosis. Thus, it was proposed that miR‑424 may serve as a tumor suppressor in HemECs, and that VEGFR‑2 may be a potential tumor suppressive target in HemECs and for the treatment of HA.

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