LncRNA DIGIT Accelerates Tube Formation of Vascular Endothelial Cells by Sponging miR-134

Abstract

Atherosclerosis is one of the most prevalent and important cardiac diseases, involving the heart and brain. This study aimed to explore the impacts of lncRNA Divergent to GSC induced by TGF-b family signaling (DIGIT) on vascular endothelial cells tube-formation capacity so as to reveal the potentials of DIGIT in atherosclerosis therapy. DIGIT expression in human microvascular endothelial HMEC-1 cells was silenced by transfection with shRNAs-targeted DIGIT. The effects of DIGIT silence on cell viability, migration, apoptosis, and tube formation were then assessed. Additionally, the cross-regulation between DIGIT and miR-134, and between miR-134 and Bmi-1 was detected to further reveal through which mechanism (s) DIGIT mediated HMEC-1 cells. The results showed that DIGIT silence significantly reduced cell viability, migration, tube-like structures formation, and induced apoptosis in HMEC-1 cells. DIGIT worked as a sponge for miR-134, and the anti-growth, anti-migratory, and anti-tube-formation functions of DIGIT silence on HMEC-1 cells were abolished by miR-134 suppression. Bmi-1 was a target of miR-134, and Bmi-1 upregulation abolished miR-134 overexpression-diminished cell growth, migration, and tube formation of HMEC-1 cells. Furthermore, Bmi-1 upregulation activated PI3K/AKT and Notch signaling pathways. In conclusion, our study demonstrated that lncRNA DIGIT accelerated tube formation of vascular endothelial cells through sponging miR-134. Our findings suggest that DIGIT and miR-134 may be promising molecular targets for atherosclerosis therapy.

<p>Knockdown of lncRNA HOXA-AS3 Suppresses the Progression of Atherosclerosis via Sponging miR-455-5p</p>

“…Atherosclerosis is one of the leading causes of myocardial infarction in the world. 1 In fact, atherosclerosis is a multistep disease, which results from multiple risk factors, 2 , 3 including dysfunction of HUVECs. 4 Various dysfunctions of HUVECs including inappropriate proliferation, migration and apoptosis are critical cellular events resulting in the occurrence and development of atherosclerosis.…”

The microRNA miR‐134‐5p induces calcium deposition by inhibiting histone deacetylase 5 in vascular smooth muscle cells

“…We were interested in miR‐134‐5p because it has been reported that it is one of the miRNAs up‐regulated in the serum of patients with coronary artery calcification 26 . Also, in endothelial cells, miR‐134‐5p is related to tumour angiogenesis 27 and endothelium‐associated cardiac tube formation during development 28 . More recently, miR‐134‐5 p was shown to be involved in VSMC phenotypic switching and migration and in the progression of thoracic aortic dissection 29 .…”

“…The function of miR‐134 has also been investigated in cardiovascular diseases, although fewer studies have been reported than for the nervous system or cancer. In the embryo, miR‐134 regulates endothelium‐linked cardiac tube formation through down‐regulation of polycomb complex protein BMI‐1 28 . Wu et al reported that miR‐134 directly targets myeloid ecotropic insertion site 2 and promotes human cardiomyocyte precursor cell proliferation 55 .…”

“…26 Also, in endothelial cells, miR-134-5p is related to tumour angiogenesis 27 and endothelium-associated cardiac tube formation during development. 28 More recently, miR-134-5p was shown to be involved in VSMC phenotypic switching and migration and in the progression of thoracic aortic dissection. 29 However, its role in calcium deposition in VSMCs has not been reported.…”

“…In the embryo, miR-134 regulates endothelium-linked cardiac tube formation through down-regulation of polycomb complex protein BMI-1. 28 Wu et al reported that miR-134 directly targets myeloid ecotropic insertion site 2 and promotes human cardiomyocyte precursor cell proliferation. 55 Indeed, miR-134 might be induced in circumstances where active cardiomyocyte proliferation is required, since it is up-regulated in acute myocardial infarction and could be an early marker of the disease.…”