Insights into circular RNAs: Biogenesis,function and their regulatory roles in cardiovascular disease

As a distinctive member of the noncoding RNA family, circular RNAs (circRNAs) are generated from single-stranded, covalently closed structures and are ubiquitous in mammalian cells and tissues. Due to its atypical circular architecture, it was conventionally deemed insignificant dark matter for a prolonged duration. Nevertheless, studies conducted over the last decade have demonstrated that this abundant, structurally stable and tissue-specific RNA has been increasingly relevant in diverse diseases, including cancer, neurological disorders, diabetes mellitus and cardiovascular diseases (CVDs). Therefore, regulatory pathways controlled by circRNAs are widely involved in the occurrence and pathological processes of CVDs through their function as miRNA sponges, protein sponges and protein scaffolds. To better understand the role of circRNAs and their complex regulatory networks in CVDs, we summarize current knowledge of their biogenesis and function and the latest research on circRNAs in CVDs, with the hope of paving the way for the identification of promising biomarkers and therapeutic strategies for CVDs.     

Circular RNA in cardiovascular disease: Expression,mechanisms and clinical prospects

Circular RNAs (circRNAs) are a group of covalently closed, endogenous, non-coding RNAs, which exist widely in human tissues including the heart. Increasing evidence has shown that cardiac circRNAs play crucial regulatory roles in cardiovascular diseases (CVDs). In this review, we aimed to provide a systemic understanding of circRNAs with a special emphasis on the cardiovascular system. We have summarized the current research on the classification, biogenesis and properties of circRNAs as well as their participation in the pathogenesis of CVDs. CircRNAs are conserved, stable and have specific spatiotemporal expression; thus, they have been accepted as a potential diagnostic marker or an incremental prognostic biomarker for CVDs.     

Prospect of circular RNA in osteogenesis: A novel orchestrator of signaling pathways

Circular RNAs (circRNAs) were initially regarded as by-products of aberrant splicing. But now, there are substantial evidence on their various roles in the regulation of genes during the development of organs and diseases. Consistent with these breakthroughs, it is experiencing rapid growth that circRNAs function as the important checkpoints during the osteogenesis. Therefore, characterizing the roles of circRNAs is useful and critical to better understanding the process of osteogenic differentiation, which could provide new avenues for the diagnosis and treatment of bone diseases, such as bone defects and osteoporosis. In this review, we presented a map of the interaction between circRNAs and the molecules of signaling pathways associated with osteogenesis, summarized the current knowledge of the biological functions of circRNAs during the osteogenic differentiation, figured out the limits of existing research works, and provided a novel look on the diagnostic and therapeutic methods of bone diseases based on circRNAs.     

Cardiovascular biomarkers in body fluids: progress and prospects in optical sensors

Cardiovascular diseases (CVD) are the major causative factors for high mortality and morbidity in developing and developed nations. The biomarker detection plays a crucial role in the early diagnosis of several non-infectious and life-threatening diseases like CVD and many cancers, which in turn will help in more successful therapy, reducing the mortality rate. Biomarkers have diagnostic, prognostic and therapeutic significances. The search for novel biomarkers using proteomics, bio-sensing, micro-fluidics, and spectroscopic techniques with good sensitivity and specificity for CVD is progressing rapidly at present, in addition to the use of gold standard biomarkers like troponin. This review is dealing with the current progress and prospects in biomarker research for the diagnosis of cardiovascular diseases.Expert opinion.Fast diagnosis of cardiovascular diseases (CVDs) can help to provide rapid medical intervention, which can affect the patient’s short and long-term health. Identification and detection of proper biomarkers for early diagnosis are crucial for successful therapy and prognosis of CVDs. The present review discusses the analysis of clinical samples such as whole blood, blood serum, and other body fluids using techniques like high-performance liquid chromatography-LASER/LED-induced fluorescence, Raman spectroscopy, mainly, optical methods, combined with nanotechnology and micro-fluidic technologies, to probe patterns of multiple markers (marker signatures) as compared to conventional techniques.     

Circulating exosomal miRNAs in cardiovascular disease pathogenesis: New emerging hopes

Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality. Standard therapies have failed to significantly increase patients’ survival. Moreover, the majority of conventional screening procedures are ineffective for the diagnosis of CVDs at early stages. Accumulating evidence suggests that numerous cell types release a class of nano-sized vesicles named exosomes into the extracellular space. Exosomes are widely distributed in various body fluids and contain a number of diverse biomolecules such as proteins, lipids, and both mRNA and noncoding RNAs which reflect host-cell molecular architecture. MicroRNAs (miRNAs), which can be found in exosomes, could be taken up by both neighboring and distal cells. Not only has recent evidence indicated the regulatory role of exosomal miRNAs in the pathogenesis of CVD, but it has also been shown that differential expression of exosomal miRNAs in CVDs has made them promising biomarkers for early detection of CVDs. Owing to these remarkable features, exosomal miRNAs have emerged as hot spots in research. This review summarizes the role of exosomal miRNAs in the pathogenesis of CVDs and discusses their potential application in the clinical setting as both therapeutic and diagnostic tools.     

circ-ZNF609: A potent circRNA in human cancers

Circular RNAs (circRNAs) are a novel group of endogenous RNAs with a circular structure. Growing evidence indicates that circRNAs are involved in a variety of human diseases including malignancies. CircRNA ZNF609 (circ-ZNF609), derived from the ZNF609 gene sequence, has been demonstrated to be involved in the development and progression of many diseases. circ-ZNF609 is thought to be a viable diagnostic and prognostic biomarker for several diseases and might be a new therapeutic target, but further research is needed to accelerate clinical application. Here, we review the biogenesis and function of circRNAs and the functional roles and molecular mechanism related to circ-ZNF609 in neoplasms and other diseases.     

Regulatory non‐coding RNAs in acute myocardial infarction

Acute myocardial infarction (AMI) is one of the most common cardiovascular diseases that leads to high mortality and morbidity globally. Various therapeutic targets for AMI have been investigated in recent years, including the non‐coding RNAs (ncRNAs). NcRNAs, a class of RNA molecules that typically do not code proteins, are divided into several subgroups. Among them, microRNAs (miRNAs) are widely studied for their modulation of several pathological aspects of AMI, including cardiomyocyte apoptosis, inflammation, angiogenesis and fibrosis. It has emerged that long ncRNAs (lncRNAs) and circular RNAs (circRNAs) also regulate these processes via interesting mechanisms. However, the regulatory functions of ncRNAs in AMI and their underlying functional mechanisms have not been systematically described. In this review, we summarize the recent findings involving ncRNA actions in AMI and briefly describe the novel mechanisms of these ncRNAs, highlighting their potential application as therapeutic targets in AMI.     

Targeting non-coding RNAs in unstable atherosclerotic plaques: Mechanism,regulation, possibilities,and limitations

Cardiovascular diseases (CVDs) caused by arteriosclerosis are the leading cause of death and disability worldwide. In the late stages of atherosclerosis, the atherosclerotic plaque gradually expands in the blood vessels, resulting in vascular stenosis. When the unstable plaque ruptures and falls off, it blocks the vessel causing vascular thrombosis, leading to strokes, myocardial infarctions, and a series of other serious diseases that endanger people''s lives. Therefore, regulating plaque stability is the main means used to address the high mortality associated with CVDs. The progression of the atherosclerotic plaque is a complex integration of vascular cell apoptosis, lipid metabolism disorders, inflammatory cell infiltration, vascular smooth muscle cell migration, and neovascular infiltration. More recently, emerging evidence has demonstrated that non-coding RNAs (ncRNAs) play a significant role in regulating the pathophysiological process of atherosclerotic plaque formation by affecting the biological functions of the vasculature and its associated cells. The purpose of this paper is to comprehensively review the regulatory mechanisms involved in the susceptibility of atherosclerotic plaque rupture, discuss the limitations of current approaches to treat plaque instability, and highlight the potential clinical value of ncRNAs as novel diagnostic biomarkers and potential therapeutic strategies to improve plaque stability and reduce the risk of major cardiovascular events.     

Exosomes in Mesenchymal Stem Cells,a New Therapeutic Strategy for Cardiovascular Diseases?

Cardiovascular diseases (CVDs) are still a major cause of people deaths worldwide, and mesenchymal stem cells (MSCs) transplantation holds great promise due to its capacity to differentiate into cardiovascular cells and secrete protective cytokines, which presents an important mechanism of MSCs therapy for CVDs. Although the capability of MSCs to differentiate into cardiomyocytes (CMCs), endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) has been well recognized in massive previous experiments both in vitro and in vivo, low survival rate of transplanted MSCs in recipient hearts suggests that therapeutic effects of MSCs transplantation might be also correlated with other underlying mechanisms. Notably, recent studies uncovered that MSCs were able to secret cholesterol-rich, phospholipid exosomes which were enriched with microRNAs (miRNAs). The released exosomes from MSCs acted on hearts and vessels, and then exerted anti-apoptosis, cardiac regeneration, anti-cardiac remodeling, anti-inflammatory effects, neovascularization and anti-vascular remodeling, which are considered as novel molecular mechanisms of therapeutic potential of MSCs transplantation. Here we summarized recent advances about the role of exosomes in MSCs therapy for CVDs, and discussed exosomes as a novel approach in the treatment of CVDs in the future.     

环状RNA的生物学功能及其在肿瘤发生中的作用

近年来,随着RNA研究技术的进步,研究者们在多种生物中发现了数量众多的环状RNA,且发现它们具有重要的生物学功能。环状RNA来源于内含子或外显子,可以充当微小RNA海绵,还能与蛋白质相结合,从而参与基因表达调控并影响蛋白质的功能,此外,个别环状RNA甚至能编码蛋白质。更重要的是,环状RNA在肿瘤(如:胃癌、肝癌、结直肠癌、乳腺癌、宫颈癌和卵巢癌等)的发生和发展过程中起着重要的调控作用。因此,环状RNA有希望成为肿瘤诊断的标志物和治疗的新靶点。     

CircRNA: a rising star in plant biology

Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules, which are widespread in eukaryotic cells. As regulatory molecules, circRNAs have various functions, such as regulating gene expression, binding miRNAs or proteins, and being translated into proteins, which are important for cell proliferation and cell differentiation, individual growth and development, as well as many other biological processes. However, compared with that in animal models, studies of circRNAs in plants lags behind and, particularly, the regulatory mechanisms of biogenesis and molecular functions of plant circRNAs remain elusive. Recent studies have shown that circRNAs are wide spread in plants with tissue- or development-specific expression patterns and are responsive to a variety of environmental stresses. In this review, we summarize these advances, focusing on the regulatory mechanisms of biogenesis, molecular and biological functions of circRNAs, and the methods for investigating circRNAs. We also discuss the challenges and the prospects of plant circRNA studies.     

Diagnostic and prognostic value of circular RNAs in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumour, which has posed a heavy health and financial burden worldwide. Due to limited symptoms at the early stage and the limitation in current biomarkers, HCC patients are usually diagnosed at the advanced stage with a pessimistic overall survival rate. Circular RNAs (circRNAs) are a subclass of single-stranded RNAs characterized by a covalently closed loop structure without 3’- or 5’-end. With advances in high-throughput sequencing technology and bioinformatics, accumulating studies have demonstrated the promotor or suppressor roles of circRNAs in the carcinogenesis, progression, and metastasis of HCC. Moreover, circRNAs are characteristic of higher abundance, stability and conservation compared with linear RNAs. Therefore, circRNAs have emerged as one of the most promising diagnostic and prognostic biomarkers for HCC with reliable accuracy, sensitivity and specificity. In this review, we briefly introduce the characteristics of circRNAs and summarize the roles of circRNAs in the biological procedures of HCC. Furthermore, we provide an overview on the potential diagnostic and prognostic value of circRNAs as biomarkers for patients with HCC. Finally, we discuss future perspectives of circRNAs in cancer research.     

Small but significant: Insights and new perspectives of exosomes in cardiovascular disease

Cardiovascular diseases (CVDs) are a major health problem worldwide, and health professionals are still actively seeking new and effective approaches for CVDs treatment. Presently, extracellular vesicles, particularly exosomes, have gained its popularity for CVDs treatment because of their function as messengers for inter‐ and extra‐cellular communications to promote cellular functions in cardiovascular system. However, as a newly developed field, researchers are still trying to fully understand the role of exosomes, and their mechanism in mediating cardiac repair process. Therefore, a comprehensive review of this topic can be timely and favourable. In this review, we summarized the basic biogenesis and characterization of exosomes and then further extended the focus on the circulating exosomes in cellular communication and stem cell‐derived exosomes in cardiac disease treatment. In addition, we covered interactions between the heart and other organs through exosomes, leading to the diagnostic characteristics of exosomes in CVDs. Future perspectives and limitations of exosomes in CVDs were also discussed with a special focus on exploring the potential delivery routes, targeting the injured tissue and engineering novel exosomes, as well as its potential as one novel target in the metabolism‐related puzzle.     

Emerging role of interleukin-13 in cardiovascular diseases: A ray of hope

Despite the great progress made in the treatment for cardiovascular diseases (CVDs), the morbidity and mortality of CVDs remains high due to the lack of effective treatment strategy. Inflammation is a central pathophysiological feature of the heart in response to both acute and chronic injury, while the molecular basis and underlying mechanisms remains obscure. Interleukin (IL)-13, a pro-inflammatory cytokine, has been known as a critical mediator in allergy and asthma. Recent studies appraise the role of IL-13 in CVDs, revealing that IL-13 is not only involved in more obvious cardiac inflammatory diseases such as myocarditis but also relevant to acute or chronic CVDs of other origins, such as myocardial infarction and heart failure. The goal of this review is to summarize the advancement in our knowledge of the regulations and functions of IL-13 in CVDs and to discuss the possible mechanisms of IL-13 involved in CVDs. We highlight that IL-13 may be a promising target for immunotherapy in CVDs.     

The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

Circular RNA (circRNA) is a novel class of single-stranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.     

Gut microbes in cardiovascular diseases and their potential therapeutic applications

Microbial ecosystem comprises a complex community in which bacteria interact with each other.The potential roles of the intestinal microbiome play in human health have gained considerable attention.The imbalance of gut microbial community has been looked to multiple chronic diseases.Cardiovascular diseases(CVDs)are leading causes of morbidity worldwide and are influ-enced by genetic and environmental factors.Recent advances have provided scientific evidence that CVD may also be attributed to gut microbiome.in this review,we highlight the complex interplay between microbes,their metabolites,and the potential influence on the generation and development of CVDs.The therapeutic potentiai of using intestinal microbiomes to treat CVD is also discussed.it is quite possible that gut microbes may be used for clinical treatments of CVD in the near future.     

Circular RNA expression alteration in whole blood of premature infants with periventricular white matter damage

Circular RNAs (circRNAs) are evolutionarily conserved and tissue-specific types of non-coding RNA and can serve as potential diagnostic biomarkers for disease. However, the clinical significance and levels of expression of circRNAs for whole blood samples of prematurely born infants afflicted by diseases such as periventricular white matter damage (PWMD) are largely unknown. Therefore, we sought to identify measures of expression of circRNAs in whole blood samples obtained from prematurely born infants afflicted by PWMD and comparatively in samples from prematurely born infants without PWMD. We found the expression levels of circRNAs which from premature with PWMD has changed. Further analysis suggests that these circRNAs have important roles in PWMD. This study can improve the understanding for the potential of the circRNAs to serve as biomarkers in PWMD. Moreover, these circRNAs may provide evidence for improving diagnosis and treatment for infants afflicted by PWMD, and merits continued research.     

Circular RNA in renal diseases

Circular RNA (circRNA) is a newly described type of non‐coding RNA. Active research is greatly enriching the current understanding of the expression and role of circRNA, and a large amount of evidence has implicated circRNA in the pathogenesis of certain renal diseases, such as renal cell carcinoma, acute kidney injury, diabetic nephropathy and lupus nephritis. Studies have found evidence that circRNAs regulate programmed cell death, invasion, and metastasis and serve as biomarkers in renal diseases. Recently, circRNAs were identified in exosomes secreted by the kidneys. Nevertheless, the function of circRNA in renal diseases remains ambiguous. Given that circRNAs are regulators of gene expression, they may be involved in the pathology of multiple renal diseases. Additionally, emerging evidence is showing that circulating circRNAs may serve as novel biomarkers for renal disease. In this review, we have summarized the identification, biogenesis, degradation, and functions of circRNA and have evaluated the roles of circRNA in renal diseases.