Abstract
Angiogenesis is a crucial process for organ morphogenesis and growth during development, and it is especially relevant during the repair of wounded tissue in adults. It is coordinated by an equilibrium of pro- and anti-angiogenic factors; nevertheless, when affected, it promotes several diseases. Lately, a growing body of evidence is indicating that non-coding RNAs (ncRNAs), such as miRNAs, circRNAs, and lncRNAs, play critical roles in angiogenesis. These ncRNAs can act in cis or trans and alter gene transcription by several mechanisms including epigenetic processes. In the following pages, we will discuss the functions of ncRNAs in the regulation of angiogenesis and neovascularization, both in normal and disease contexts, from an epigenetic perspective. Additionally, we will describe the contribution of Next-Generation Sequencing (NGS) techniques to the discovery and understanding of the role of ncRNAs in angiogenesis.
Highlights
In the vascular network, blood vessels act as channels for nutrients, oxygen delivery, and metabolic waste evacuation
The expression of many angiogenesis-related genes involved in the vascular endothelial growth factor (VEGF) signaling pathway is regulated through long non-coding RNAs (lncRNAs), and recently, researchers discovered that some of them perform their regulatory function by influencing the expression and activity of several epigenetic modulators [20, 22]
A study performed by Wang and colleagues in 2014 revealed that there was cooperation between VEGF and miRNAs in coronary artery disease (CAD) progression. They performed smRNA-seq and identified EPCspecific miRNome that was related to angiogenic processes, which suggests that miRNAs in endothelial progenitor cells (EPCs) with a poor capacity to enhance angiogenesis might have higher levels of miRNAs targeting VEGF
Summary
Blood vessels act as channels for nutrients, oxygen delivery, and metabolic waste evacuation. The incorporation of ncRNAs as epigenetic elements has opened up new fields of study in which they have been shown to regulate gene expression. EZH2 is associated with the formation of heterochromatin and can affect multiple target genes such as Vasohibin 1 (VASH1), which functions as a negative feedback modulator of angiogenesis in vascular endothelial cells [56, 57] (Figure 1B).
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