The Landscape of Noncoding RNA in Pulmonary Hypertension

Abstract

The transcriptome of pulmonary hypertension (PH) is complex and highly genetically heterogeneous, with noncoding RNA transcripts playing crucial roles. The majority of RNAs in the noncoding transcriptome are long noncoding RNAs (lncRNAs) with less circular RNAs (circRNAs), which are two characteristics gaining increasing attention in the forefront of RNA research field. These noncoding transcripts (especially lncRNAs and circRNAs) exert important regulatory functions in PH and emerge as potential disease biomarkers and therapeutic targets. Recent technological advancements have established great momentum for discovery and functional characterization of ncRNAs, which include broad transcriptome sequencing such as bulk RNA-sequence, single-cell and spatial transcriptomics, and RNA-protein/RNA interactions. In this review, we summarize the current research on the classification, biogenesis, and the biological functions and molecular mechanisms of these noncoding RNAs (ncRNAs) involved in the pulmonary vascular remodeling in PH. Furthermore, we highlight the utility and challenges of using these ncRNAs as biomarkers and therapeutics in PH.

Co-profiling reveals distinct patterns of genomic chromatin accessibility and gene expression in pulmonary hypertension caused by chronic hypoxia

“…1 B), non-coding transcripts from these regions in the genome can be a relevant alterative mechanism underlying aberrant gene expressions. The non-coding transcripts can regulate transcriptional gene expression or modulate mRNA stability [ 7 ]. An additional post-transcriptional regulation includes the RNA-binding proteins in mastering gene expression profiles [ 8 ].…”

Advances in Research on the Regulatory Roles of lncRNAs in Osteoarthritic Cartilage

“…The identification of the lncRNA molecules and the investigation of its action mechanism provide new insights into the occurrence and development of diseases, in addition to the discovery of new approaches for the diagnosis and treatment of diseases. LncRNA molecules had hitherto been considered biomarkers for diagnostic and therapeutic targets in cancer, pulmonary hypertension, autoimmune diseases, and other diseases [ 129 , 130 , 131 ]. After an in-depth study of lncRNAs in the pathogenesis of osteoarthritis, researchers discovered that the expression of lncRNAs differs between OA patients and healthy individuals.…”

Potential Involvement of LncRNAs in Cardiometabolic Diseases

“…Pulmonary hypertension is caused by high pressure in the blood vessels from the heart to the lungs, which affects both the lungs and the heart [106,107]. It is characterized by pathological changes to signaling pathways (e.g., endothelin, nitric oxide, prostacyclin, transforming growth factor β (TGFB) signaling pathways) [108,109], and a number of lncR-NAs have been identified to play key roles in these signaling pathways [110][111][112][113]. Besides binding to miRNAs and RNA-binding proteins, lncRNAs can interact with DNA to regulate the binding of epigenetic and/or transcription factors to the genome, thereby, regulating epitranscriptomic and/or transcriptomic changes (Figure 4B).…”