A Roadmap for Fixing the Heart: RNA Regulatory Networks in Cardiac Disease

Abstract

With the continuous development of RNA biology and massive genome-wide transcriptome analysis, more and more RNA molecules and their functions have been explored in the last decade. Increasing evidence has demonstrated that RNArelated regulatory networks play an important role in a variety of human diseases, including cardiovascular diseases. In this review, we focus on RNA regulatory networks in heart disease, most of which are devastating conditions with no known cure. We systemically summarize recent discoveries of important new components of RNA regulatory networks, including microRNAs, long non-coding RNAs, and circular RNAs, as well as multiple regulators that affect the activity of these networks in cardiac physiology and pathology. In addition, this review covers emerging micropeptides, which represent short open reading frames (sORFs) in long non-coding RNA transcripts that may modulate cardiac physiology. Based on the current knowledge of RNA regulatory networks, we think that ongoing discoveries will not only provide us a better understanding of the molecular mechanisms that underlie heart disease, but will also identify novel biomarkers and therapeutic targets for the diagnosis and treatment of cardiac disease.ncRNAs Play Important Roles in Heart Disease miRNAs Mediate Post-Transcriptional Regulation of Gene Expression in Heart Disease miRNAs are small, single-stranded ncRNAs with a length of 20-22 nt, which play a crucial role in regulating posttranscriptional gene expression by guiding their target mRNAs to the RNA-induced silencing complex (RISC). 8 Lin-4 of C. elegans was the first

Circ_0065149 Alleviates Oxidized Low-Density Lipoprotein-Induced Apoptosis and Inflammation in Atherosclerosis by Targeting miR-330-5p

“…Recent evidence suggests that circRNAs play a crucial role in the development of a variety of heart diseases ( Zhang et al, 2018 ; Altesha et al, 2019 ; Tang et al, 2020 ). Deep RNA sequencing of cardiac tissue revealed differential expression of circRNAs in the heart ( Tan et al, 2017 ).…”

Emerging Role of Adipocyte Dysfunction in Inducing Heart Failure Among Obese Patients With Prediabetes and Known Diabetes Mellitus

“…In addition, adipocytes, cardiac myocytes, the vasculature, and immune cells in AO and DM are connected with each other through specific ECVs carrying nucleic acids, proteins, lipids, and cellular metabolites ( 204 ). Although the number of various subtypes of ECVs especially originated from endothelial cells correlated well with BMI and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) ( 205 ), there are a limiting number of non-coding RNAs, such as hsa-miR-423-5p, rno-miR-16, rno-miR-20b, rno-miR-93, rno-miR-106b, rno-miR-223, hsa-miR-660-3p, hsa-miR-665, hsa-miR-1285-3p, and hsa-miR-4491, which was strongly associated with the development of HFpEF ( 206 ). Some of the muscle-specific circulating miRNAs (hsa-miR-423-5p, rno-miR-16, rno-miR-20b) and others contribute to interstitial fibrosis (hsa-miR-665, hsa-miR-1285-3p, and hsa-miR-4491), IR (miR-141-3p), and inflammation (miR-4763-3p) ( 24 ).…”

The lncRNA Malat1 regulates microvascular function after myocardial infarction in mice via miR-26b-5p/Mfn1 axis-mediated mitochondrial dynamics

“…Long non-coding RNAs (lncRNAs) are RNA molecules that do not possess protein-coding potential. Nevertheless, this RNA subgroup has been demonstrated to play crucial roles in the pathogenesis of many cardiovascular disorders, including MI, hypertension, and arrhythmia [ 2 , 3 ]. The lncRNA Malat1 is one of the most promising members involved in the angiogenic process of various diseases, such as diabetic foot ulcer, diabetic retinopathy, and central nervous system injury [ [4] , [5] , [6] ].…”