Abstract

Non-coding RNAs (ncRNAs) are involved in various cellular processes. There are several ncRNA classes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). The detailed roles of these molecules in pulmonary hypertension (PH) remain unclear. We systematically collected and reviewed reports describing the functions of ncRNAs (miRNAs, lncRNAs, and circRNAs) in PH through database retrieval and manual literature reading. The characteristics of identified articles, especially the experimental methods, were carefully reviewed. Furthermore, regulatory networks were constructed using ncRNAs and their interacting RNAs or genes. These data were extracted from studies on pulmonary arterial smooth muscle cells, pulmonary artery endothelial cells, and pulmonary artery fibroblasts. We included 14 lncRNAs, 1 circRNA, 74 miRNAs, and 110 mRNAs in the constructed networks. Using these networks, herein, we describe the current knowledge on the role of ncRNAs in PH. Moreover, these networks actively provide an improved understanding of the roles of ncRNAs in PH. The results of this study are crucial for the clinical application of ncRNAs.

Highlights

  • Pulmonary hypertension (PH) is a serious disease characterized by progressively increased pulmonary vascular resistance and pulmonary artery pressure; the diagnostic criterion is mean pulmonary artery pressure ≥25 mmHg (Galiè et al, 2016; Weber et al, 2018)

  • Studies were selected when the following criteria were met: 1) the study reported pathogenic roles of miRNAs, long non-coding RNAs (lncRNAs), and/ or circRNAs in pulmonary hypertension (PH); 2) mechanistic studies were performed in pulmonary arterial smooth muscle cells (PASMCs), pulmonary artery endothelial cells (PAECs), and/or pulmonary artery fibroblasts (PAFs); and 3) the relationships between ncRNAs and their interacting RNAs or genes were experimentally identified via luciferase reporter assay, western blot, and/or qPCR

  • In this article, we reviewed the published literature to search for functional miRNAs, lncRNAs, and circRNAs in PH

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Summary

INTRODUCTION

Pulmonary hypertension (PH) is a serious disease characterized by progressively increased pulmonary vascular resistance and pulmonary artery pressure; the diagnostic criterion is mean pulmonary artery pressure ≥25 mmHg (Galiè et al, 2016; Weber et al, 2018). Studies were selected when the following criteria were met: 1) the study reported pathogenic roles of miRNAs, lncRNAs, and/ or circRNAs in PH; 2) mechanistic studies were performed in pulmonary arterial smooth muscle cells (PASMCs), pulmonary artery endothelial cells (PAECs), and/or pulmonary artery fibroblasts (PAFs); and 3) the relationships between ncRNAs and their interacting RNAs or genes were experimentally identified via luciferase reporter assay, western blot, and/or qPCR. Using these criteria returned 140 qualified articles (Figure 1).

General Characteristics of Qualified Articles
Construction of Non-coding RNA Regulatory Networks
General Characteristics of the Constructed Networks
Functional Enrichment Analysis
Key Non-coding RNA Subnetworks
ENVIRONMENTAL FACTORS IN PULMONARY HYPERTENSION
POTENTIAL APPLICATIONS OF NON-CODING RNAS
Findings
CONCLUSION
Full Text
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