R nba circ1/16/2024 ![]() postulated that all endogenous RNA transcripts sharing common miRNA response elements (MREs) can communicate with and regulate each other through competition for a limited pool of miRNAs ( 17). The theoretical and practical development of the artificial miRNA sponge laid an important foundation for the ceRNA hypothesis. The sponging constructs are not only invaluable tools for miRNA loss-of-function studies in vitro and in vivo, but also critical for the development of RNA-based therapeutic applications ( 15, 16). These synthetic miRNA sponges are usually expressed from strong promoters, engineered to carry multiple binding sites for a miRNA or miRNA family of interest and have been shown to derepress miRNA targets both in vitro and in vivo ( 14). Several years before the discovery of ceRNAs, or natural miRNA sponges, many studies had found that artificial miRNA sponges were able to specifically and effectively inhibit miRNA activity ( 14– 16). Here, we reviewed the role of circRNAs as ceRNAs in atherosclerosis, myocardial infarction, cardiac fibrosis, heart failure, aneurysm, and stroke, with a special focus on the molecular mechanism, which provides a new direction for further research on the pathogenesis and treatment of CVDs. Recent studies have identified circRNAs as ceRNAs in many diseases including CVDs ( 11– 13). Although the functions of most circRNAs remain elusive, a select number of circRNAs are known to function as competitive endogenous RNAs (ceRNAs) by decoying miRNAs from other target transcripts, thereby controlling gene expression at the posttranscriptional level ( 10). Indeed, circRNAs are diverse, abundant, and expressed in a tissue- and developmental stage-specific manner ( 5, 8). In recent years, advances in the high-throughput sequencing technology and circRNA-specific bioinformatics algorithms have resulted in the discovery and identification of thousands of circRNAs ( 5– 9). However, they were mainly considered to be errors of the normal splicing process and did not receive much attention ( 4). A few years later, circRNAs were observed by electron microscopy in the cytoplasmic fractions of eukaryotic cells ( 3). To develop novel preventive and therapeutic strategies, we should elucidate and understand the underlying molecular mechanisms of these diseases.Ĭircular RNAs (circRNAs) were first discovered in plant viroids more than 40 years ago ( 2). Current treatments primarily alleviate symptoms or slow down disease progression. CVDs are still the leading cause of death worldwide ( 1). Despite improvements in pharmacotherapy and surgical interventions, as well as lifestyle modifications, morbidity and mortality in patients with CVDs remain high in recent years ( 1). Here, we review the progress in studying the role of circRNAs as ceRNAs in CVDs, with emphasis on the molecular mechanism, and discuss future directions and possible clinical implications.Ĭardiovascular and cerebrovascular diseases (CVDs) are general terms used to refer to all cardiac and cerebral diseases related to vasculopathy. Understanding the underlying molecular mechanism could aid the discovery of therapeutic targets or strategies against CVDs. The role of circRNAs as ceRNAs in the pathogenesis of cardiovascular and cerebrovascular diseases (CVDs) has been recently reported and highlighted. CircRNAs can competitively bind to miRNAs and abolish the suppressive effect of miRNAs on target RNAs, thus regulating gene expression at the posttranscriptional level. Accumulating evidence indicates that circRNA plays an important role in the biological functions of a network of competing endogenous RNA (ceRNA). This unusual class of RNA species is generated by a back-splicing event of exons or introns, resulting in a covalently closed circRNA molecule. 2Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang, ChinaĬircular RNAs (circRNAs) represent a novel class of widespread and diverse endogenous RNA molecules.1Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan, China.Xue Min 1 Dong-liang Liu 1 Xing-dong Xiong 1,2 *
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