Circular RNAs in pulmonary hypertension: Emerging biological concepts and potential mechanism

Abstract

Circular RNAs (circRNAs) are endogenous RNAs with a covalently closed single‐stranded transcript. They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets. Using the most powerful RNA sequencing and bioinformatics techniques, a large number of circRNAs have been identified and further functional studies have been performed. It is known that circRNAs act as potential biomarkers, sponges for microRNAs (miRNAs) and RNA‐binding proteins (RBPs), and regulators of mRNA transcription. They also participate in the translation of peptides or proteins. Many types of circRNAs are dysregulated in plasma or lung tissues, and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs), leading to pulmonary vascular remodeling in pulmonary hypertension (PH). One possible mechanism is that circRNAs can regulate the function of PAECs and PASMCs by acting as miRNA sponge. However, other potential mechanisms of action of circRNAs are still being actively explored in PH. This paper presents a systematic review of the biogenesis, biological characterization, relevant underlying functions, and future perspectives for studies of circRNAs in the pathogenesis of PH.

Exosomal circular RNAs: Biogenesis, effect, and application in cardiovascular diseases

“…Our previous review summarizes the discovery and research history of circRNAs ( Wang et al, 2022 ). Briefly, these single-stranded closed RNAs were first identified in the genome of potato spindle in 1971 ( Diener, 1971 ).…”

The Landscape of Noncoding RNA in Pulmonary Hypertension

“…Aside from miRNAs, lncRNAs and circRNAs are other two major groups of ncRNAs relatively less investigated and understood in the PH field. However, they are attracting growing attention due to their abundance, regulatory functional roles, cell/tissue expression specificity in human diseases, and potential therapeutic targets and disease biomarkers [ 18 , 19 , 20 , 21 ]. This review focuses on the recent developments of lncRNA and circRNA related to PH.…”

“…Following biogenesis, most circRNAs are exported to the cytoplasm, with the exception of intron-containing circRNAs [ 118 ]. The dysregulation of circRNAs has been shown to be involved in various pathophysiological conditions and has attracted growing interest in the scientific research of cardiovascular disease [ 119 ], including PH [ 18 ].…”

“…In addition, circRNA can function in trans as ceRNAs binding to miRNAs [ 124 ], directly interacting with regulator proteins [ 125 ], regulating gene expression (e.g., epigenetic control, splicing, transcription, and translation) [ 126 ], and encoding peptides or proteins [ 127 ]. There has been an increasing focus on characterizing disease relevance and functional mechanisms of circRNA in PH due to their emerging potential as promising therapeutic targets [ 18 ]. However, our knowledge of circRNA, either in biogenesis or functional or the pathophysiological roles in the human disease, is still in its infancy.…”

Regulatory T Cell-Related Gene Indicators in Pulmonary Hypertension

“…Pulmonary hypertension (PH) is a cardiopulmonary disorder characterized by progressive occlusion of the distal pulmonary arteries and increased pulmonary vascular resistance ultimately leading to right heart failure and even death ( Hassoun, 2021 ). The pathogenesis of PH is driven or initiated by multiple elements such as genetic predisposition ( Morrell et al, 2019 ; Wang et al, 2020 ), epigenetic alterations ( Potus et al, 2020 ; Yan et al, 2020 ; Wang Q. et al, 2022 ), inflammation ( Rabinovitch et al, 2014 ; Liang et al, 2021 ), altered metabolism ( He et al, 2020 ; He Y.-y. et al, 2021 ; Xu et al, 2021 ; Wang S. et al, 2022 ), and environmental cues such as hypoxia ( He Y.-Y.…”