• Angiogenesis
• Cardiovascular disease
• Circular RNA
• Exosome
• Long non-coding RNA
• MicroRNA
• Non-coding RNAs

• Humans
• Cardiovascular Diseases/genetics
• Cardiovascular Diseases/metabolism
• Cardiovascular Diseases/pathology
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• RNA, Untranslated/genetics
• RNA, Untranslated/metabolism
• Neovascularization, Pathologic/genetics
• Neovascularization, Pathologic/metabolism
• Animals
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Circular/genetics
• RNA, Circular/metabolism
• Neovascularization, Physiologic/genetics
• Angiogenesis

• 3D-printed technolgy
• Exosome
• Gelma
• Mesenchymal stem cell
• Phenotypic switch
• Vascular smooth muscle cells

• Exosomes/metabolism
• Aortic Dissection
• Ferroptosis/drug effects
• Printing, Three-Dimensional
• Animals
• Hydrogels/chemistry
• Mesenchymal Stem Cells/metabolism
• Muscle, Smooth, Vascular
• Myocytes, Smooth Muscle/drug effects
• Mice
• Gelatin/chemistry
• Cell Proliferation/drug effects
• Humans
• Male
• Mice, Inbred C57BL
• Rats
• Aorta
• Cell Movement/drug effects

• 81970399 the project of the National Natural Science Foundation
• 20190901008JC Basic Department of Jilin Provincial Science and Technology Department
• 2021JC043 Jilin Province Health Science and Technology Capability Enhancement Project
• 212553HJ010288477 Jilin Province Science and Technology Development Plan Project

• Circular RNA
• Exosome
• Lung adenocarcinoma
• Pleural effusion
• Tuberculosis

• Humans
• RNA, Circular/genetics
• RNA, Circular/metabolism
• Adenocarcinoma of Lung/genetics
• Lung Neoplasms/genetics
• Pleural Effusion, Malignant/genetics
• Cross-Sectional Studies
• Pleural Effusion/genetics
• Pleural Effusion/metabolism
• Male
• Female
• Middle Aged
• Tuberculosis, Pleural/genetics
• Tuberculosis, Pleural/diagnosis
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Clinical Relevance

Circular RNAs (circRNAs), a new star of noncoding RNAs, are a group of endogenous RNAs that form a covalently closed circle and occur widely in the mammalian genome. Most circRNAs are conserved throughout species and frequently show stage-specific expression during various stages of tissue development. CircRNAs were a mystery discovery, as they were initially believed to be a product of splicing errors; however, subsequent research has shown that circRNAs can perform various functions and help in the regulation of splicing and transcription, including playing a role as microRNA (miRNA) sponges. With the application of high throughput next-generation technologies, circRNA hotspots were discovered. There are emerging indications that explain the association of circRNAs with human diseases, like cancers, developmental disorders, and inflammation, and circRNAs may be a new potential biomarker for the diagnosis and treatment outcome of various diseases, including cancer. After the discoveries of miRNAs and long noncoding RNAs, circRNAs are now acting as a novel research entity of interest in the field of RNA disease biology. In this review, we aim to focus on major updates on the biogeny and metabolism of circRNAs, along with their possible/established roles in major human diseases.

• Circular RNAs
• Cancer
• MicroRNA sponges
• Biomarkers
• Long noncoding RNA
• RNA biology

• Cause-of-death analysis
• Estimation of age
• Identification of monozygotic twins
• Identification of tissues and body fluids
• Time-related estimation
• miRNA
• ncRNA

• Humans
• Male
• MicroRNAs/genetics
• RNA, Long Noncoding/genetics
• RNA, Circular
• Piwi-Interacting RNA
• RNA, Untranslated
• Forensic Medicine

• 81672887 National Natural Science Foundation of China

• biomarkers
• cardiovascular diseases
• diagnosis
• extracellular vesicles
• intercellular communication
• prognosis

• Humans
• Cardiovascular Diseases/metabolism
• Extracellular Vesicles/metabolism
• Signal Transduction
• Cell Communication/physiology
• Heart Diseases/metabolism

• (PID2022-138163OB-C32) Ministry of Education and Science of the Spanish Government
• CTS-466 Junta de Andalucía Regional Council.

• cardiovascular disease
• diagnosis
• exosome
• miRNA
• prognosis

• diagnostic markers
• molecular medicine

• cardiovascular disease
• circRNA
• exosomes
• lncRNA
• miRNA
• ncRNA

• Humans
• Exosomes/genetics
• Cardiovascular Diseases/genetics
• Cardiovascular Diseases/therapy
• RNA, Untranslated/genetics
• Biomarkers
• Cardiovascular System

Heart failure is a major global health concern. Noncoding RNAs (ncRNAs) are involved in physiological processes and in the pathogenesis of various diseases, including heart failure. ncRNAs have emerged as critical components of transcriptional regulatory pathways that govern cardiac development, stress response, signaling, and remodeling in cardiac pathology. Recently, studies of ncRNAs in cardiovascular disease have achieved significant development. Here, we discuss the roles of ncRNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) that modulate the cardiac hypertrophy and heart failure.

Myocardial infarction (MI) is a complicated pathology triggered by numerous environmental and genetic factors. Understanding the effect of epigenetic regulation mechanisms on the cardiovascular disease would advance the field and promote prophylactic methods targeting epigenetic mechanisms. Genetic screening guides individualised MI therapies and surveillance. The present review reported the latest development on the epigenetic regulation of MI in terms of DNA methylation, histone modifications, and microRNA-dependent MI mechanisms and the novel therapies based on epigenetics.

• DNA methylation DNA
• cardiovascular
• epigenetics
• histone modifications
• micro-RNA
• myocardial infarction
• non-coding RNAs rna

In order to explore the role of exosomal circRNAs in the occurrence and development of sepsis, we looked for potential diagnostic markers to accurately identify sepsis and to lay a molecular basis for precise treatment. Ultracentrifugation was used to extract exosomes from the serum of patients with sepsis and healthy individuals. Then, changes in circRNA expression in exosomes were studied by circRNA microarray analysis. Gene ontology (GO) analysis and Kyoto City Encyclopaedia of Genes and Genomes (KEGG) pathway analysis were used to annotate the biological functions and pathways of genes, and a circRNA-miRNA-mRNA regulatory network was constructed. In the microarray analysis, 132 circRNAs were significantly differentially expressed, including 80 and 52 that were upregulated and downregulated, respectively. RT-qPCR verified the results of microarray analysis: hsa_circRNA_104484 and hsa_circRNA_104670 were upregulated in sepsis serum exosomes. ROC analysis showed that hsa_circRNA_104484 and hsa_circRNA_104670 in serum exosomes have the potential to be used as diagnostic markers for sepsis. The circRNA-miRNA-mRNA network predicted the potential regulatory pathways of differentially expressed circRNAs. There are differences in the expression of circRNA in serum exosomes between patients with sepsis and healthy individuals, which may be involved in the occurrence and development of the disease. Among them, elevations in hsa_circRNA_104484 and hsa_circRNA_104670 could be used as novel diagnostic biomarkers and molecular therapeutic targets.

Glioma (GM) is the most common type of malignant brain tumor with a high recurrence rate. Circular RNAs (circRNAs) play a key role in mediating tumorigenesis. However, the functions and mechanisms of circRNAs in GM are still not fully understood. A circRNA microarray was performed to identify differentially expressed circRNAs in GM and non-cancerous specimens. Reverse transcription-quantitative PCR was used to detect circ-aspartyl/asparaginyl β-hydroxylase (ASPH) expression in GM tissues and cells. The clinical importance of circ-ASPH was investigated using Kaplan-Meier analysis. The functions of circ-ASPH were investigated in LN229 and U87MG cells. Bioinformatics, RNA immunoprecipitation, RNA pull-down and luciferase reporter assays were used to explore the mechanisms of circ-ASPH in GM. circ-ASPH levels were upregulated in GM specimens and cells. The prognostic role of circ-ASPH was identified in patients with GM. Loss/gain of function assays demonstrated that circ-ASPH increased cell proliferation, migration and invasion in GM cells. Mechanistically, circ-ASPH counteracted microRNA (miR)-599-mediated androgen receptor (AR) suppression by acting as a sponge for miR-599. Rescue assays indicated that circ-ASPH facilitated cell progression by regulating AR expression. Moreover, AR activated long non-coding RNA suppressor of cytokine signaling 2-antisense RNA 1 (SOCS2-AS1) expression in GM cells. Taken together, circ-ASPH/miR-599/AR/SOCS2-AS1 signaling may be a promising biomarker/therapeutic target for GM.

• SOCS2-AS1
• circ-ASPH
• circular RNA
• glioma
• miR-599

Sudden cardiac death (SCD) caused by acute ischemic heart disease (IHD) is a major cause of sudden death worldwide. Circular RNAs (circRNAs) are abundant in the heart and play important roles in cardiovascular diseases, but the role of circRNAs as biomarkers in the forensic diagnosis of SCD caused by acute IHD remains poorly characterized. To investigate the potential of two heart-enriched circRNAs, circNFIX and circSLC8A1, we explored the expression of these two circRNAs in different kinds of commonly used IHD models, and further verified their expressions in forensic autopsy cases. The results from both the IHD rat and H9c2 cell models revealed that circSlc8a1 level was upregulated, while the circNfix level was elevated in the early stage of ischemia and subsequently downregulated. The time-dependent expression patterns of the two circRNAs suggested their potential as SCD biomarkers. In autopsy cases, the results showed that the expression of these two circRNAs in the myocardium with acute IHD-related SCDs corresponded to the observations in the ischemic models. Further analysis related to myocardial ischemia indicated that circSLC8A1 showed high sensitivity and specificity for myocardial infarction and was positively correlated with creatine kinase MB in pericardial fluid. Downregulated circNFIX level could indicate the ischemic myocardial damage, and it was negatively correlated with the coronary artery stenosis grade. The combination of circSLC8A1 and circNFIX had better performance to discriminate IHD-related SCDs. The results suggested that circSLC8A1 and circNFIX may be used as auxiliary diagnostic markers for SCD caused by acute IHD in forensic medicine.

The prevention and diagnosis of sudden cardiac death (SCD) are among the most important keystones and challenges in clinical and forensic practice. However, the diagnostic value of the current biomarkers remains unresolved issues. Therefore, novel diagnostic biomarkers are urgently required to identify patients with early-stage cardiovascular diseases (CVD), and to assist in the postmortem diagnosis of SCD cases without typical cardiac damage. An increasing number of studies show that circular RNAs (circRNAs) have stable expressions in myocardial tissue, and their time- and tissue-specific expression levels might reflect the pathophysiological status of the heart, which makes them potential CVD biomarkers. In this article, we briefly introduced the biogenesis and functional characteristics of circRNAs. Moreover, we described the roles of circRNAs in multiple SCD-related diseases, including coronary artery disease (CAD), myocardial ischemia or infarction, arrhythmia, cardiomyopathy, and myocarditis, and discussed the application prospects and challenges of circRNAs as a novel biomarker in the clinical and forensic diagnosis of SCD.

• biomarker
• circular RNA
• diagnosis
• forensic
• sudden cardiac death

• Epigenetics
• acute myocardial infraction
• coronary artery disease (CAD)
• precision medicine
• therapeutic targets

• Department of Biotechnology (DBT), Govt. of India

It was reported that circular RNAs (circRNAs) and microRNAs (miRNAs) were related to non-small cell lung cancer (NSCLC) development. However, the detailed mechanisms of circ_0020123 and miR-384 in NSCLC are elusive.

QRT-PCR and Western blot assay were performed to detect the transcription and protein levels of genes, respectively. Then, the functional experiments, including MTT assay, flow cytometry, and transwell assay, were employed. Besides, the interaction between miR-384 and circ_0020123 or tripartite motif‑containing protein 44 (TRIM44) was predicted by starbase or targetscan, and then verified by the dual-luciferase reporter, RNA pull-down assays and RNA immunoprecipitation assay (RIP). Mouse xenograft assay was performed to evaluate the effect of circ_0020123 on tumor growth in vivo.

Levels of circ_0020123 and TRIM44 were enhanced, and the miR-384 level was attenuated in NSCLC tissues and cells. Circ_0020123 depletion attenuated the abilities of NSCLC cell viability, migration, invasion, and epithelial–mesenchymal transition (EMT), and induced apoptosis. Besides, circ_0020123 interacted with miR-384, and miR-384 targeted TRIM44. Circ_0020123 regulated cell progression by regulating miR-384 and subsequently mediated TRIM44 expression. Besides, circ_0020123 depletion repressed tumor growth in vivo.

We demonstrated that circ_0020123 knockdown suppressed NSCLC cell progression by regulating the miR-384/TRIM44 axis, providing the theoretical basis for the therapy of NSCLC.

• NSCLC
• TRIM44
• cell growth
• circ_0020123
• miR-384

• Competing endogenous RNA
• Intrauterine adhesions
• RNA-sequencing
• circPlekha7

• Animals
• Apoptosis
• Carrier Proteins/genetics
• Carrier Proteins/metabolism
• Cell Proliferation
• Computational Biology
• Endometrium/metabolism
• Epithelial Cells/metabolism
• Female
• Fibrosis
• Gene Expression Profiling
• Gene Expression Regulation
• RNA, Circular
• RNA-Seq
• Rats
• Smad3 Protein/antagonists & inhibitors
• Stromal Cells/metabolism
• Tissue Adhesions/metabolism
• Transforming Growth Factor beta1/biosynthesis
• Transforming Growth Factor beta1/metabolism

• autophagy
• cardiovascular diseases
• circRNA
• lncRNA
• miRNA

• CircRNAs
• coronary artery samples
• coronary heart disease
• qRT-PCR

Circular RNAs (circRNAs) are circularized, single-stranded RNAs that are covalently linked. With their abundance in tissues and developmental stage-specific expression, circRNAs participate in a variety of physiological and pathological processes. In this review, we discuss the development of circRNAs used as biomarkers and therapeutic targets for cardiovascular diseases (CVDs), focusing on recent discoveries and applications of exosomal circRNAs that highlight opportunities and challenges. Some studies have identified a spectrum of circRNAs that are differentially expressed in CVDs, while other studies further manipulated specific circRNA expression and showed an ameliorated pathogenic state such as ischemic injury, hypertrophy, and cardiac fibrosis. Studies and applications of circRNAs are being rapidly developed. We expect to see clinical use of circRNAs as biomarkers and targets for disease treatment in the near future.

Circular RNAs (circRNAs) are categorized as non-coding RNAs that, unlike widely known canonical linear RNAs, form a covalently closed continuous loop without 5′ or 3′ polarities, which enables them to resist digestion by RNA exonucleases. Although the functions of circRNAs remain largely unknown, accumulated evidence has demonstrated that circRNAs can act as microRNA sponges, which allows them to regulate numerous biological processes and disease mechanisms, including apoptosis, angiogenesis, invasion, metastasis and stem cell differentiation. Although research into circRNAs is in its infancy, studies have identified critical roles for circRNAs in the initiation and progression of disease. The present study delineated the characteristics and functions of circRNAs, and focused on the potential relationship between circRNAs and osteonecrosis of the femoral head (ONFH). CircRNAs represent a novel avenue for studying the mechanisms underlying ONFH as well as possible treatments.