Circular RNAs as potential biomarkers and therapeutics for cardiovascular disease

Abstract

Circular RNAs (circRNAs) are genetic regulators that were earlier considered as “junk”. In contrast to linear RNAs, they have covalently linked ends with no polyadenylated tails. CircRNAs can act as RNA-binding proteins, sequestering agents, transcriptional regulators, as well as microRNA sponges. In addition, it is reported that some selected circRNAs are transformed into functional proteins. These RNA molecules always circularize through covalent bonds, and their presence has been demonstrated across species. They are usually abundant and stable as well as evolutionarily conserved in tissues (liver, lung, stomach), saliva, exosomes, and blood. Therefore, they have been proposed as the “next big thing” in molecular biomarkers for several diseases, particularly in cancer. Recently, circRNAs have been investigated in cardiovascular diseases (CVD) and reported to play important roles in heart failure, coronary artery disease, and myocardial infarction. Here, we review the recent literature and discuss the impact and the diagnostic and prognostic values of circRNAs in CVD.

Circular RNAs and Its Biological Functions in Health and Disease

“…Cardiovascular disease (CVD) is one of the most important health problems. It causes most of the deaths worldwide [35]. According to recent studies, a number of circRNAs may play a significant role during development of CVD or pathological conditions such as cardiac hypertrophy, coronary artery disease, atherosclerotic vascular disease, cardiomyopathy, cardiac fibrosis, heart failure (HF), ischemia, and myocardial infarction (MI) [36][37][38].…”

“…In addition, circRNA serves as a protein scaffold such as circAmotl1 in cardiac dysfunction [35,43]. circAmotl1 facilitates phosphorylation of protein kinase B (AKT) and nuclear translocation of pAKT by forming ternary complexes with AKT and phosphoinositide-dependent protein kinase (PDK) [43][44][45].…”

The potential roles of circular RNAs in osteonecrosis of the femoral head (Review)

“…These two methods can form exon circrnas (exon sequence only, ecircrnas), intron circrnas (composed of intron sequences, cirnas) and exon-intron circrnas (exon and intron sequences, eicirnas) ( Fig. 1); ecircrnas account for >80% of total circrnas (26). The 3' end of the upstream exon of the precursor mrna is covalently linked to the 5' end of the downstream exon by a reverse splicing process, after which the intron is cleaved to form an ecircrna.…”

Kardiyovasküler Hastalıklarda Uzun Kodlamayan RNA’lar ve Sirküler RNA’ların Önemi

“…Genel olarak circRNA'lar sitoplazmada depolanmaktadır, çok küçük bir kısmı ise çekirdekte bulunmaktadır. 6 Nukleusta sentezlenen pre-mRNA' dan kırpılmalar ile mRNA ve dairesel yapıdaki circRNA oluşumu temel olarak Şekil 4' de şematik olarak gösterilmiştir. Küçük nükleer ribonükleoproteinler (snRNP'ler) tarafından pre-mRNA'ların intronları kesilir ve doğrusal mRNA'lardan farklı olarak kesilmiş segmentteki 5'-uç, 3'-uçla birleşerek dairesel hale gelerek circRNA'ları oluşturmaktadır.…”

“…KVH'ın temelinde yer alan ateroskleroz, lipid birikimi ve fibroz plaklar ile karakterize edilen kronik bir patolojidir. Kodlamayan RNA molekülleri ile kardiyovasküler hastalıklar arasında bağlantıyı anlayabilmek ve yeni terapötik hedefler geliştirebilmek için kardiyovasküler hastalıkların başlangıcında, ilerlemesinde ve modülasyonunda rol alan lncRNA'lar 5 ve circRNA'lar 6 gibi kodlamayan RNA'ların tanımlanması önem taşımaktadır.…”