miR‑3133 inhibits proliferation and angiogenesis by targeting the JUNB/VEGF pathway in human umbilical vein endothelial cells

Xu,Mengdie; Cao,Lin; Zhang,Xiaokang; Zhuang,Yu; Zhang,Ying; Wang,Qinzhi; Chen,Yansu; Xu,Lichun; Sun,Guixiang

doi:10.3892/or.2020.7715

miR‑3133 inhibits proliferation and angiogenesis by targeting the JUNB/VEGF pathway in human umbilical vein endothelial cells

Authors:
- Mengdie Xu
- Lin Cao
- Xiaokang Zhang
- Yu Zhuang
- Ying Zhang
- Qinzhi Wang
- Yansu Chen
- Lichun Xu
- Guixiang Sun
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Affiliations: School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China
Published online on: August 4, 2020 https://doi.org/10.3892/or.2020.7715
Pages: 1699-1708

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Abstract

Membranous obstruction of the inferior vena cava (MOVC) has the highest incidence rate among the different types of Budd‑Chiari syndrome (BCS) in China. The inferior vena cava septum of patients with MOVC contains capillaries and the two surfaces of the membrane are composed of vascular endothelial tissue. Membrane formation occurs due to endothelial damage. MicroRNAs (miRNAs/miRs) have been verified to be involved in the pathogenesis and progression of various human diseases. A previous study by our group suggested that miR‑3133 was downregulated in the serum of patients with MOVC. In the present study, the possible mechanistic implication of miR‑3133 in MOVC‑associated processes was further explored. It was observed that miR‑3133 overexpression inhibited, whereas miR‑3133 knockdown enhanced the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the CCK‑8 and tube formation assays. JUNB, a member of activator protein 1 and an important upstream transcriptional molecule of vascular endothelial growth factor (VEGF), was proven to be a direct target gene of miR‑3133 using a bioinformatics prediction and luciferase reporter assay. Meanwhile, the mRNA and protein expression of JUNB and VEGF was determined by PCR, ELISA and western blot analyses. Of note, miR‑3133 overexpression downregulated, while miR‑3133 knockdown elevated the expression of JUNB and VEGF significantly. Furthermore, it was demonstrated that JUNB upregulated the expression and secretion of VEGF to promote HUVEC proliferation and angiogenesis. miR‑3133 was able to inhibit the effect of JUNB overexpression to promote cell proliferation, angiogenesis and the expression of VEGF. In conclusion, the present study demonstrated that miR‑3133 regulated endothelial cell proliferation and angiogenesis through the JUNB/VEGF pathway, which may provide an approach for inhibiting diaphragm formation of the inferior vena cava in MOVC.

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