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

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.

Extracellular vesicles‐transmitted long non‐coding RNA MTUS2‐5 promotes proliferation and vascularization of human vascular endothelial cells in patients with Budd–Chiari syndrome

“…Vascular endothelial growth factor can modulate the proliferation and angiogenesis of vascular endothelial cells and significantly correlate with thrombogenesis 32 . A study by Mengdie Xu's 5 team found that VEGF is a target for the regulation of HUVECs. The results from our study present the high secretion of VEGF from HUVECs when treated with overexpressing lncRNA MTUS2‐5 transfection or EVs from BCS patients, which is consistent with these previous studies.…”

“…Thrombosis with increased blood viscosity is considered to be the most common pathophysiological mechanism 4 . Aberrant expression of vascular endothelial growth factor (VEGF) and relative cytokines was reported in the serum of patients with membranous obstruction of the inferior vena cava (MOVC), which is the main type of BCS in China 5,6 . Therefore, the formation of the inferior vena cava diaphragm probably starts from proliferation and angiogenesis of vascular endothelial cells.…”

JunB condensation attenuates vascular endothelial damage under hyperglycemic condition

“…As a TF, JunB is implicated in the regulation of the VEGF signaling pathway, the differentiation of Th2 and Th17 cells, and the expression of human papillomavirus e6 and e7 oncoproteins ( Rengarajan et al., 2002 ; Henderson et al., 2004 ; Schmidt et al., 2007 ; He and Luo, 2012 ; Carr et al., 2017 ; Hasan et al., 2017 ; Yoshitomi et al., 2017 ; Xu et al., 2020 ). It has been reported that individual or multiple TFs form intracellular mono- or multi-element condensates to regulate the corresponding transcriptional activities ( Smith et al., 2021 ).…”

To identify biomarkers associated with the transfer of diabetes combined with cancer in human genes using bioinformatics analysis

“…JUNB is an ER-dependent gene found only in premenopausal women. [ 38 , 39 ] The JUNB gene has been shown to play an important role in the advancement of hepatocellular carcinoma and lung cancer and it is strongly associated with patient survival, suggesting a novel function of JUNB in cell proliferation and tumor aggressiveness. [ 40 , 41 ] We discovered little convincing evidence for the JUNB gene in our search of the literature, and therefore, the bioinformatics analysis performed in this study increases our understanding of this gene.…”