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Background: Increasingly studies highlight the crucial role of the ancestral retrovirus envelope protein ERVWE1 in the pathogenic mechanisms of schizophrenia, a severe psychiatric disorder affecting approximately 1% of the global population. Recent studies also underscore the significance of circular RNAs (circRNAs), crucial for neurogenesis and synaptogenesis, in maintaining neuronal functions. However, the precise relationship between ERVWE1 and circRNAs in the etiology of schizophrenia remains elusive. Results: This study observed elevated levels of hsa_circ_0001810 (circ_0001810) in the blood samples of schizophrenia patients, displaying a significant positive correlation with ERVWE1 expression. Interestingly, in vivo studies demonstrated that ERVWE1 upregulated circ_0001810 in neuronal cells. Circ_0001810, acting as a competing endogenous RNA (ceRNA), bound to miR-1197 and facilitated the release of adenylate kinase 2 (AK2). The bioinformatics analysis of the schizophrenia datasets revealed increased levels of AK2 and enrichment of mitochondrial dynamics. Notably, miR-1197 was reduced in schizophrenia patients, while AK2 levels were increased. Additionally, AK2 showed positive correlations with ERVWE1 and circ_0001810. Further studies demonstrated that AK2 led to mitochondrial dysfunction, characterized by loss of intracellular ATP, mitochondrial depolarization, and disruption of mitochondrial dynamics. Our comprehensive investigation suggested that ERVWE1 influenced ATP levels, promoted mitochondrial depolarization, and disrupted mitochondrial dynamics through the circ_0001810/AK2 pathway. Conclusions: Circ_0001810 and AK2 were increased in schizophrenia and positively correlated with ERVWE1. Importantly, ERVWE1 triggered mitochondrial dysfunction through circ_0001810/miR-1197/AK2 pathway. Recent focus on the impact of mitochondrial dynamics on schizophrenia development had led to our discovery of a novel mechanism by which ERVWE1 contributed to the etiology of schizophrenia, particularly through mitochondrial dynamics. Moreover, these findings collectively proposed that circ_0001810 might serve as a potential blood-based biomarker for schizophrenia. Consistent with our previous theories, ERVWE1 is increasingly recognized as a promising therapeutic target for schizophrenia. [ABSTRACT FROM AUTHOR]

[Display omitted] • This study is the first attempt to clarify the role of circRNA in surgical ventricular reconstruction (SVR). • We identified a novel circRNA, named circMap4k2, is preferentially expressed in myocardial tissue and significantly up-regulated in response to SVR. • We confirmed that circMap4k2 promotes cardiomyocyte proliferation, and also enhances cardiac regeneration in the plication zone of SVR and thus attenuate residual cardiac remodelling. • CircMap4k2 prompts cardiac regeneration through miR-106a-3p/Azin1 pathway. • This work would provide opportunity to search new therapeutic approach for advanced heart failure. Surgical ventricular reconstruction (SVR) is an alternative therapeutic approach in patients with refractory heart failure (HF), but residual remodeling after SVR limits the improvement of HF. Recently, we reported that SVR may act as an environmental cue to reactivate endogenous proliferation of cardiomyocytes; however, it is unclear whether enhancing endogenous cardiomyocyte regeneration further improves HF after SVR. We aimed to explore whether circular RNAs (circRNAs) would involved in SVR and their mechanisms. Male C57BL/6 mice were subjected to myocardial infarction (MI) or sham surgery. Four weeks later, MI mice with a large ventricular aneurysm underwent SVR or a second open-chest operation only. Echocardiography and histological analysis were used to evaluate heart function, cardiac remodeling, and myocardial regeneration. Sequencing of circular RNAs, RNA immunoprecipitation, RNA pulldown, and luciferase reporter assay were used to explore the underlying mechanisms. SVR markedly attenuated cardiac remodeling and induced cardiomyocyte regeneration, as evidenced by positive staining of Ki-67, phospho-histone H3 (pH3), and Aurora B in the plication zone, but significant residual remodeling still existed in comparison with the sham group. Sequencing results showed that SVR altered the expression profile of cardiac circRNAs, and circMap4k2 was identified as the most upregulated one. After characterizing circMap4k2, we noted that overexpression of circMap4k2 significantly promoted proliferation of cardiomyocytes in cultured neonatal rat cardiomyocytes and silencing of circMap4k2 significantly inhibited it; similar results were obtained in SVR-treated MI mice but not in MI mice without SVR treatment. Residual cardiac remodeling after SVR was further attenuated by circMap4k2 overexpression. CircMap4k2 bound with miR-106a-3p and inhibited cardiomyocyte proliferation by targeting a downstream effector of the antizyme inhibitor 1 (Azin1) gene. CircMap4k2 acts as an environmental cue and targets the miR-106a-3p/Azin1 pathway to increase cardiac regeneration in the plication zone and attenuate residual remodeling after SVR. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is one of the most prevalent diseases of central nervous system that is caused by degeneration of the substantia nigra's dopamine-producing neurons through apoptosis. Apoptosis is regulated by initiators' and executioners' caspases both in intrinsic and extrinsic pathways, further resulting in neuronal damage. In that context, targeting apoptosis appears as a promising therapeutic approach for treating neurodegenerative diseases. Non-coding RNAs—more especially, microRNAs, or miRNAs—are a promising target for the therapy of neurodegenerative diseases because they are essential for a number of cellular processes, including signaling, apoptosis, cell proliferation, and gene regulation. It is estimated that a substantial portion of coding genes (more than 60%) are regulated by miRNAs. These small regulatory molecules can have wide-reaching consequences on cellular processes like apoptosis, both in terms of intrinsic and extrinsic pathways. Furthermore, it was recommended that a disruption in miRNA expression levels could also result in perturbation of typical apoptosis pathways, which may be a factor in certain diseases like PD. The latest research on miRNAs and their impact on neural cell injury in PD models by regulating the apoptosis pathway is summarized in this review article. Furthermore, the importance of lncRNA/circRNA-miRNA-mRNA network for regulating apoptosis pathways in PD models and treatment is explored. These results can be utilized for developing new strategies in PD treatment. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have been recognized as pivotal regulators in tumorigenesis, yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma (HCC) remain elusive. We sought to unveil the expression profile and biological role of circMYBL2 in HCC. Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells, and qRTPCR analysis was then performed in HCC cell lines and tissues, revealing significant upregulation of circMYBL2. Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression. Furthermore, bioinformatics analysis, qRT-PCR analysis, luciferase reporter assays, and western blot analysis were employed to investigate the interplay among circMYBL2, miR-1205, and E2F1. CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines. Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells, whereas circMYBL2 knockdown elicited contrasting effects. Mechanistically, our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205. Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis, suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) have emerged as a prominent class of covalently closed single-stranded RNA molecules that exhibit tissue-specific expression and potential as biomarkers in extracellular vesicles (EVs) derived from liquid biopsies. Still, their characteristics and applications in EVs remain to be unveiled. Methods: We performed a comprehensive analysis of EV-derived circRNAs (EV-circRNAs) using transcriptomics data obtained from 1082 human body fluids, including plasma, urine, cerebrospinal fluid (CSF), and bile. Our validation strategy utilized RT-qPCR and RNA immunoprecipitation assays, complemented by computational techniques for analyzing EV-circRNA features and RNA-binding protein interactions. Results: We identified 136,327 EV-circRNAs from various human body fluids. Significantly, a considerable amount of circRNAs with a high back-splicing ratio are highly enriched in EVs compared to linear RNAs. Additionally, we discovered brain-specific circRNAs enriched in plasma EVs and cancer-associated EV-circRNAs linked to clinical outcomes. Moreover, we demonstrated that EV-circRNAs have the potential to serve as biomarkers for evaluating immunotherapy efficacy in non-small cell lung cancer (NSCLC). Importantly, we identified the involvement of RBPs, particularly YBX1, in the sorting mechanism of circRNAs into EVs. Conclusions: This study unveils the extensive repertoire of EV-circRNAs across human biofluids, offering insights into their potential as disease biomarkers and their mechanistic roles within EVs. The identification of specific circRNAs and the elucidation of RBP-mediated sorting mechanisms open new avenues for the clinical application of EV-circRNAs in disease diagnostics and therapeutics. [ABSTRACT FROM AUTHOR]

Apelin, a bioactive peptide that serves as an endogenous ligand for the apelin receptor (APJ), is overexpressed in various types of cancers and contributes to cancer cell proliferation, viability, migration, angiogenesis, and metastasis, as well as immune deviation. Noncoding RNAs (ncRNAs) regulate gene expression, and there is growing evidence suggesting a bidirectional crosstalk between ncRNAs (including long noncoding RNAs [lncRNAs], circular RNAs [circRNAs], and microRNAs [miRNAs]) and apelin in cancers. Certain miRNAs can directly target the apelin and inhibit its expression, thereby suppressing tumor growth. It has been indicated that miR‐224, miR‐195/miR‐195‐5p, miR‐204‐5p, miR‐631, miR‐4286, miR‐637, miR‐4493, and miR‐214‐3p target apelin mRNA and influence its expression in prostate cancer, lung cancer, esophageal cancer, chondrosarcoma, melanoma, gastric cancer, glioma, and hepatocellular carcinoma (HCC), respectively. Moreover, circ‐NOTCH1, circ‐ZNF264, and lncRNA BACE1‐AS upregulate apelin expression in gastric cancer, glioma, and HCC, respectively. On the other hand, apelin has been shown to regulate the expression of certain ncRNAs to affect tumorigenesis. It was revealed that apelin affects the expression of circ_0000004/miR‐1303, miR‐15a‐5p, and miR‐106a‐5p in osteosarcoma, lung cancer, and prostate cancer, respectively. This review explains a bidirectional interplay between ncRNAs and apelin in cancers to provide insights concerning the molecular mechanisms underlying this crosstalk and potential implications for cancer therapy. Significance: This manuscript highlights the critical role of apelin, a bioactive peptide, in various cancers and its interplay with ncRNAs. Understanding the bidirectional crosstalk between apelin and ncRNAs, including lncRNAs, circRNAs, and miRNAs, is pivotal for uncovering the molecular mechanisms underlying cancer progression. The identification of specific miRNAs and ncRNAs that target or regulate apelin in different cancers opens new avenues for therapeutic interventions. This review offers significant insights into how targeting the apelin‐ncRNA axis could potentially lead to innovative cancer treatments. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a demyelinating autoimmune disease characterized by early onset, for which the interaction of genetic and environmental factors is crucial. Dysregulation of the immune system as well as myelinization-de-myelinization has been shown to correlate with changes in RNA, including non-coding RNAs. Recently, circular RNAs (circRNAs) have emerged as a key player in the complex network of gene dysregulation associated with MS. Despite several efforts, the mechanisms driving circRNA regulation and dysregulation in MS still need to be properly elucidated. Here, we explore the panorama of circRNA expression in PBMCs purified from five newly diagnosed MS patients and five healthy controls (HCs) using the Arraystar Human circRNAs microarray. Experimental validation was then carried out in a validation cohort, and a possible correlation with disease severity was tested. We identified 64 differentially expressed circRNAs, 53 of which were downregulated in PBMCs purified from MS compared to the HCs. The discovery dataset was subsequently validated using qRT-PCR with an independent cohort of 20 RRMS patients and 20 HCs. We validated seven circRNAs differentially expressed in the RRMS group versus the HC group. hsa_circ_0000518, hsa_circ_0000517, hsa_circ_0000514, and hsa_circ_0000511 were significantly upregulated in the MS group, while hsa_circ_0018905, hsa_circ_0048764, and hsa_circ_0003445 were significantly downregulated; Among them, the expression level of hsa_circ_0018905 was significantly decreased in patients showing a higher level of disability and in progressive forms of MS. We described the circRNAs expression profile of PBMCs in newly diagnosed MS patients and proposed hsa_circ_0018905 as potential MS biomarker. [ABSTRACT FROM AUTHOR]

Objectives: The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) remains not fully understood. Our previous studies demonstrated that miR‐21‐5p may participate in the TMJOA development and the interaction between circRNA‐ACAP2 (CircACAP2) and miR‐21‐5p. Our present study aimed to explore the biological functions and regulatory mechanisms of CircACAP2 in TMJOA. Materials and Methods: The differential expression pattern of CircACAP2 in OA and normal tissues or cells was detected. CircACAP2 biological functions experiments were performed in chondrocytes by overexpression and interference techniques. The interaction of CircACAP2 with miR‐21‐5p and downstream target mRNA, polymorphic adenoma gene 1 (PLAG1), was predicted by bioinformatic databases and then demonstrated by dual‐luciferase reporter assay. The biological role of CircACAP2 in TMJOA was investigated and validated in a mouse model. Results: The expression level of CircACAP2 was markedly reduced in OA cartilage and directly related to chondrocyte proliferation and apoptosis as well as ECM metabolism in the cartilage. CircACAP2 functioned in chondrocytes via targeting miR‐21‐5p and PLAG1. Overexpressing of CircACAP2 alleviated TMJOA in mouse models. Conclusions: The present study unveiled that CircACAP2/miR‐21‐5p/PLAG1 axis may play an important regulatory role in TMJOA progression, which may highlight a potentially effective intervention and therapeutic strategy for the treatment of TMJOA. [ABSTRACT FROM AUTHOR]

Circular RNAs are emerging players in human cancers, including esophageal squamous cell carcinoma (ESCC). Herein, we assessed the expression level of circ_0023990 and explored the molecular mechanisms of circ_0023990 in ESCC. circ_0023990, miR-6884-5p, and PAK1 expressions in ESCC tissues and cells were detected by quantitative real-time polymerase chain reaction and western blot. ESCC cells were transfected with different constructs to alter the expression of circ_0023990, miR-6884-5p, and PAK1. The effect of circ_0023990 on the proliferation, invasion, and glycolysis of ESCC cells was observed. The interaction between circ_0023990 and miR-6884-5p and between miR-6884-5p and PAK1 were explored. A mouse model of ESCC was established to study the in vivo effect of circ_0023990 knockdown on tumor formation.The expression levels of circ_0023990 was upregulated in ESCC tissues and cells. Inhibiting circ_0023990 suppressed the proliferation, invasion, and glycolysis of ESCC cells. circ_0023990 might target miR-6884-5p and consequently modulate the expression and activity of PAK1. Knockdown of circ_0023990 led to significantly reduced tumor volume and weight in mice with ESCC.These findings overall suggest an oncogenic role of circ_0023990 in ESCC. Future research is warranted to confirm the expression pattern and clinical significance of circ_0023990 in ESCC. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) regulate gene expression and biological procedures by controlling target genes or downstream pathways by sponging their related miRNA (s). Three types of circRNAs have been identified; exonic circRNAs (ecircRNAs), intronic RNAs (ciRNAs), and exon-intron circRNAs (ElciRNAs). It is clarified that altered levels of circRNAs have dynamic pathological and physiological functions in kidney diseases. Evidence suggests that circRNAs can be considered novel diagnostic biomarkers and therapeutic targets for renal diseases. Glomerulonephritis (GN) is a general term used to refer to a wide range of glomerular diseases. GN is an important cause of chronic kidney diseases. Here, we review the biogenesis of circRNAs, and their molecular and physiological functions in the kidney. Moreover, the dysregulated expression of circRNAs and their biological functions are discussed in primary and secondary glomerulonephritis. Moreover, diagnostic and therapeutic values of circRNAs in distinguishing or treating different types of GN are highlighted. [ABSTRACT FROM AUTHOR]

Objectives: Non-coding RNA (ncRNA) plays a role in the development of diabetes and coronary heart disease. However, there is limited research on the association between ncRNA and these conditions. This study aims to conduct a bibliometric analysis and visualization of existing research to provide a comprehensive reference for future investigation in this field. Methods: We searched the China National Knowledge Infrastructure (CNKI) and Web of Science Core Collection (WoSCC) databases for articles published from 2012 to 2024. We analyzed publication volume, country of origin, authors, and keywords using Microsoft Office Excel, CiteSpace, and VOSviewer. Results: A total of 414 papers from 56 countries/regions, involving 298 authors, were analyzed. China had the highest number of publications (177), followed by the USA (90) and Italy (28). The number of publications generally shows an increasing trend. Collaborative research efforts were prevalent, with Katare Rajesh being the most cited author on average. International Journal of Molecular Sciences emerged as the most prolific journal in this field, while the article "MicroRNA profiling unveils hyperglycaemic memory in the diabetic heart" was identified as the most frequently cited. The analysis of keywords and literature indicates that current research predominantly focuses on the expression and mechanisms of ncRNA in disease, as well as its potential as a biomarker. Conclusion: Research on ncRNA in the context of diabetes and coronary heart disease has made notable strides, although it warrants further exploration. Through bibliometric and visual analysis, we elucidate the collaborative relationships among researchers, which can facilitate the identification of potential collaborators. Additionally, we delineate the key areas and emergent trends in this field, providing valuable insights that can guide researchers in selecting future research directions. Plain Language Summary: Tables and pictures are used to show the research status of ncRNA in diabetes mellitus with coronary heart disease This research explores the connection between a type of RNA called ncRNA and two common diseases: diabetes and coronary heart disease. We used a method called bibliometrics to analyze over 400 research papers published on this topic from 2012 to 2024. What we found: • The number of studies on ncRNA and diabetes with heart disease has been increasing over the past 12 years, indicating growing interest in this area. • China and the United States have published the most research on this topic, but international collaboration could further enhance the impact of these studies. • Some scientists, like Rajesh Katare, have made significant contributions to this field with their research on miRNA as a potential biomarker for heart disease in diabetes patients. • The most common journals publishing research on this topic include the International Journal of Molecular Sciences and the Journal of the American College of Cardiology. • The main focus of current research is understanding how ncRNA is expressed and functions in these diseases, and its potential as a biomarker for early diagnosis and treatment. Why this is important: • Diabetes and coronary heart disease are major health problems worldwide, causing significant illness and death. • ncRNA has the potential to be used as a biomarker for these diseases, which could lead to earlier diagnosis and better treatment options. • Understanding the role of ncRNA in these diseases could also help develop new treatments that target the underlying causes of the diseases. What's next: • Future research should focus on understanding the role of long noncoding RNA in diabetes and heart disease, as this type of RNA is thought to be important in regulating genes related to these diseases. • Increased international collaboration could. help further advance the field and improve the impact of research findings. [ABSTRACT FROM AUTHOR]

Background: While small extracellular vesicles (sEVs)-derived circular RNAs (circRNAs) have been emerged as significant players in cancer, the function and underlying mechanism of sEVs-derived circRNAs in anti-cancer immunity remain unclear. Methods: Gastric cancer (GC)-derived circRNAs were identified using RNA-seq data from GEO datasets and quantitative reverse transcription polymerase chain reaction (qRT-PCR), RNA immunoprecipitation, dual-luciferase assay, and bioinformatics analysis were performed to investigate the regulatory axis. Transwell assay, wound healing assay, cell counting kit-8 (CCK-8) assay, and xenograft models were used to evaluate its role in GC progression in vivo and in vitro. The delivery of specific circRNAs into sEVs were verified through electron microscopy, nanoparticle tracking analysis (NTA) and fuorescence in situ hybridization (FISH). Flow cytometric analysis and immunohistochemical staining were conducted to find out how specific circRNAs mediated CD8+ T cell exhaustion and resistant to anti-programmed cell death 1 (PD-1) therapy. Results: We identified that circ_0001947, packaged by GC-derived sEVs, was obviously elevated in GC and was associated with poor clinical outcome. High circ0001947 level augmented the proliferation, migration, and invasion of GC cells. Mechanistically, circ0001947 sponged miR−661 and miR−671−5p to promote the expression of CD39, which further facilitated CD8+ T cell exhaustion and immune resistance. Conversely, blocking circ_0001947 attenuated CD8+ T cell exhaustion and increased the response to anti-PD−1 therapy. Conclusions: Our study manifested the therapeutic potential of targeting sEVs-transmitted circ_0001947 to prohibit CD8+ T cell exhaustion and immune resistance in GC. [ABSTRACT FROM AUTHOR]

Lung cancer treatment and detection can be improved by the identification of new biomarkers. Novel approaches in investigating circular RNAs (circRNAs) as biomarkers have yielded promising results. A circRNA molecule circHIPK3 was found to be widely expressed in non-small-cell lung cancer (NSCLC) cells, where it plays a crucial role in lung cancer tumorigenesis. CircHIPK3 promotes lung cancer progression by sponging oncosuppressive miRNAs such as miR-124, miR-381-3p, miR-149, and miR-107, which results in increased cell proliferation, migration, and resistance to therapies. Inhibiting circHIPK3 has been demonstrated to suppress tumour growth and induce apoptosis, which suggests its potential use in the development of new lung cancer treatment strategies targeting circHIPK3-related pathways. As a biomarker, circHIPK3 shows promise for early detection and monitoring of lung cancer. CircHIPK3 increased expression levels in lung cancer cells, and its potential link to metastasis risk highlights its clinical relevance. Given the promising preliminary findings, more clinical trials are needed to validate circHIPK3 efficacy as a biomarker. Moreover, future research should determine if the mechanisms discovered in NSCLC apply to small cell lung cancer (SCLC) to investigate circHIPK3-targeted therapies for SCLC. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a unique class of RNA molecules formed through back‐splicing rather than linear splicing. As an emerging field in molecular biology, circRNAs have garnered significant attention due to their distinct structure and potential functional implications. A comprehensive understanding of circRNAs' functions and potential clinical applications remains elusive despite accumulating evidence of their involvement in disease pathogenesis. Recent research highlights their significant roles in various human diseases, but comprehensive reviews on their functions and applications remain scarce. This review provides an in‐depth examination of circRNAs, focusing first on their involvement in non‐neoplastic diseases such as respiratory, endocrine, metabolic, musculoskeletal, cardiovascular, and renal disorders. We then explore their roles in tumors, with particular emphasis on exosomal circular RNAs, which are crucial for cancer initiation, progression, and resistance to treatment. By detailing their biogenesis, functions, and impact on disease mechanisms, this review underscores the potential of circRNAs as diagnostic biomarkers and therapeutic targets. The review not only enhances our understanding of circRNAs' roles in specific diseases and tumor types but also highlights their potential as novel diagnostic and therapeutic tools, thereby paving the way for future clinical investigations and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Abstract Background Increasingly studies highlight the crucial role of the ancestral retrovirus envelope protein ERVWE1 in the pathogenic mechanisms of schizophrenia, a severe psychiatric disorder affecting approximately 1% of the global population. Recent studies also underscore the significance of circular RNAs (circRNAs), crucial for neurogenesis and synaptogenesis, in maintaining neuronal functions. However, the precise relationship between ERVWE1 and circRNAs in the etiology of schizophrenia remains elusive. Results This study observed elevated levels of hsa_circ_0001810 (circ_0001810) in the blood samples of schizophrenia patients, displaying a significant positive correlation with ERVWE1 expression. Interestingly, in vivo studies demonstrated that ERVWE1 upregulated circ_0001810 in neuronal cells. Circ_0001810, acting as a competing endogenous RNA (ceRNA), bound to miR-1197 and facilitated the release of adenylate kinase 2 (AK2). The bioinformatics analysis of the schizophrenia datasets revealed increased levels of AK2 and enrichment of mitochondrial dynamics. Notably, miR-1197 was reduced in schizophrenia patients, while AK2 levels were increased. Additionally, AK2 showed positive correlations with ERVWE1 and circ_0001810. Further studies demonstrated that AK2 led to mitochondrial dysfunction, characterized by loss of intracellular ATP, mitochondrial depolarization, and disruption of mitochondrial dynamics. Our comprehensive investigation suggested that ERVWE1 influenced ATP levels, promoted mitochondrial depolarization, and disrupted mitochondrial dynamics through the circ_0001810/AK2 pathway. Conclusions Circ_0001810 and AK2 were increased in schizophrenia and positively correlated with ERVWE1. Importantly, ERVWE1 triggered mitochondrial dysfunction through circ_0001810/miR-1197/AK2 pathway. Recent focus on the impact of mitochondrial dynamics on schizophrenia development had led to our discovery of a novel mechanism by which ERVWE1 contributed to the etiology of schizophrenia, particularly through mitochondrial dynamics. Moreover, these findings collectively proposed that circ_0001810 might serve as a potential blood-based biomarker for schizophrenia. Consistent with our previous theories, ERVWE1 is increasingly recognized as a promising therapeutic target for schizophrenia.

Introduction: Surgical ventricular reconstruction (SVR) is an alternative therapeutic approach in patients with refractory heart failure (HF), but residual remodeling after SVR limits the improvement of HF. Recently, we reported that SVR may act as an environmental cue to reactivate endogenous proliferation of cardiomyocytes; however, it is unclear whether enhancing endogenous cardiomyocyte regeneration further improves HF after SVR. Objectives: We aimed to explore whether circular RNAs (circRNAs) would involved in SVR and their mechanisms. Methods: Male C57BL/6 mice were subjected to myocardial infarction (MI) or sham surgery. Four weeks later, MI mice with a large ventricular aneurysm underwent SVR or a second open-chest operation only. Echocardiography and histological analysis were used to evaluate heart function, cardiac remodeling, and myocardial regeneration. Sequencing of circular RNAs, RNA immunoprecipitation, RNA pulldown, and luciferase reporter assay were used to explore the underlying mechanisms. Results: SVR markedly attenuated cardiac remodeling and induced cardiomyocyte regeneration, as evidenced by positive staining of Ki-67, phospho-histone H3 (pH3), and Aurora B in the plication zone, but significant residual remodeling still existed in comparison with the sham group. Sequencing results showed that SVR altered the expression profile of cardiac circRNAs, and circMap4k2 was identified as the most upregulated one. After characterizing circMap4k2, we noted that overexpression of circMap4k2 significantly promoted proliferation of cardiomyocytes in cultured neonatal rat cardiomyocytes and silencing of circMap4k2 significantly inhibited it; similar results were obtained in SVR-treated MI mice but not in MI mice without SVR treatment. Residual cardiac remodeling after SVR was further attenuated by circMap4k2 overexpression. CircMap4k2 bound with miR-106a-3p and inhibited cardiomyocyte proliferation by targeting a downstream effector of the antizyme inhibitor 1 (Azin1) gene. Conclusions: CircMap4k2 acts as an environmental cue and targets the miR-106a-3p/Azin1 pathway to increase cardiac regeneration in the plication zone and attenuate residual remodeling after SVR.

Abstract Background Circular RNAs (circRNAs) have emerged as a prominent class of covalently closed single-stranded RNA molecules that exhibit tissue-specific expression and potential as biomarkers in extracellular vesicles (EVs) derived from liquid biopsies. Still, their characteristics and applications in EVs remain to be unveiled. Methods We performed a comprehensive analysis of EV-derived circRNAs (EV-circRNAs) using transcriptomics data obtained from 1082 human body fluids, including plasma, urine, cerebrospinal fluid (CSF), and bile. Our validation strategy utilized RT-qPCR and RNA immunoprecipitation assays, complemented by computational techniques for analyzing EV-circRNA features and RNA-binding protein interactions. Results We identified 136,327 EV-circRNAs from various human body fluids. Significantly, a considerable amount of circRNAs with a high back-splicing ratio are highly enriched in EVs compared to linear RNAs. Additionally, we discovered brain-specific circRNAs enriched in plasma EVs and cancer-associated EV-circRNAs linked to clinical outcomes. Moreover, we demonstrated that EV-circRNAs have the potential to serve as biomarkers for evaluating immunotherapy efficacy in non-small cell lung cancer (NSCLC). Importantly, we identified the involvement of RBPs, particularly YBX1, in the sorting mechanism of circRNAs into EVs. Conclusions This study unveils the extensive repertoire of EV-circRNAs across human biofluids, offering insights into their potential as disease biomarkers and their mechanistic roles within EVs. The identification of specific circRNAs and the elucidation of RBP-mediated sorting mechanisms open new avenues for the clinical application of EV-circRNAs in disease diagnostics and therapeutics.

Abstract Objectives To investigate the roles of Ca2+ influx-regulated circular RNAs (circRNAs) in T cells from patients with systemic lupus erythematosus (SLE). Methods The expression profile of circRNAs in Jurkat cells, co-cultured with and without ionomycin, was analyzed by next-generation sequencing and validated using real-time polymerase chain reaction. The identified Ca2+ influx-regulated circRNAs were further examined in T cells from 42 patients with SLE and 23 healthy controls. The biological function of specific circRNA was investigated using transfection and RNA pull-down assay. Results After validation, we confirmed that the expression levels of circ-ERCC4, circ-NFATC2, circ-MYH10, circ-CAMTA1, circ-ASH1L, circ-SOCS7, and circ-ASAP1 were consistently increased in Jurkat cells following Ca2+ influx. The expression levels of circ-CAMTA1, circ-ASH1L, and circ-ASAP1 were significantly lower in T cells from patients with SLE, with even lower levels observed in those with higher disease activity. Interferon (IFN)-α was found to suppress the expression of circ-CAMTA1. Circ-CAMTA1 bound to pyruvate carboxylase and inhibited its biological activity. Overexpression of circ-CAMTA1, but not its linear form, significantly decreased extracellular glucose levels. Furthermore, increased expression of circ-CAMTA1, but not its linear form, decreased miR-181c-5p expression, resulting increased IL-2 secretion. Conclusion Three Ca2+ influx-regulated circ-RNAs—circ-CAMTA1, circ-ASH1L, and circ-ASAP1 —were significantly reduced in T cells from patients with SLE and associated with disease activity. IFN-α suppressed the expression of circ-CAMTA1, which interacted with pyruvate carboxylase, inhibited its activity, affected glucose metabolism, and increased IL-2 secretion. These findings suggest that circ-CAMTA1 regulated by Ca²⁺ influx modulated T cell function in patients with SLE.

Abstract Background While small extracellular vesicles (sEVs)-derived circular RNAs (circRNAs) have been emerged as significant players in cancer, the function and underlying mechanism of sEVs-derived circRNAs in anti-cancer immunity remain unclear. Methods Gastric cancer (GC)-derived circRNAs were identified using RNA-seq data from GEO datasets and quantitative reverse transcription polymerase chain reaction (qRT-PCR), RNA immunoprecipitation, dual-luciferase assay, and bioinformatics analysis were performed to investigate the regulatory axis. Transwell assay, wound healing assay, cell counting kit-8 (CCK-8) assay, and xenograft models were used to evaluate its role in GC progression in vivo and in vitro. The delivery of specific circRNAs into sEVs were verified through electron microscopy, nanoparticle tracking analysis (NTA) and fuorescence in situ hybridization (FISH). Flow cytometric analysis and immunohistochemical staining were conducted to find out how specific circRNAs mediated CD8+ T cell exhaustion and resistant to anti-programmed cell death 1 (PD-1) therapy. Results We identified that circ_0001947, packaged by GC-derived sEVs, was obviously elevated in GC and was associated with poor clinical outcome. High circ0001947 level augmented the proliferation, migration, and invasion of GC cells. Mechanistically, circ0001947 sponged miR−661 and miR−671−5p to promote the expression of CD39, which further facilitated CD8+ T cell exhaustion and immune resistance. Conversely, blocking circ_0001947 attenuated CD8+ T cell exhaustion and increased the response to anti-PD−1 therapy. Conclusions Our study manifested the therapeutic potential of targeting sEVs-transmitted circ_0001947 to prohibit CD8+ T cell exhaustion and immune resistance in GC.

From a global perspective, cardiovascular diseases (CVDs), the leading factor accounting for population mortality, and circRNAs, RNA molecules with stable closed-loop structures, have been proven to be closely related. The latent clinical value and the potential role of circRNAs in CVDs have been attracting increasing, active research interest, but bibliometric studies in this field are still lacking. Thus, in this study, we conducted a bibliometric analysis by using software such as VOSviewer, CiteSpace, Microsoft Excel, and the R package to determine the current research progress and hotspots and ultimately provide an overview of the development trends and future frontiers in this field. In our study, based on our search strategy, a total of 1206 publications published before July 31, 2023 were accessed from the WOSCC database. According to our findings, there is a notable increasing trend in global publications in the field of circRNA in CVDs. China was found to be the dominant country in terms of publication number, but a lack of high-quality articles was a significant fault. A cluster analysis on the co-cited references indicated that dilated cardiomyopathy, AMI, and cardiac hypertrophy are the greatest objects of concern. In contrast, a keywords analysis indicated that high importance has been ascribed to MI, abdominal aortic aneurysm, cell proliferation, and coronary artery diseases.

Acute ischemic stroke is a clinical emergency and a condition with high morbidity, mortality, and disability. Accurate predictive, diagnostic, and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined. With innovations in high-throughput gene sequencing analysis, many aberrantly expressed non-coding RNAs (ncRNAs) in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models. Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes, leading to neuroprotection or deterioration, thus ncRNAs can serve as therapeutic targets in acute ischemic stroke. Moreover, distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. In particular, ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke. In this review, we consolidate the latest progress of research into the roles of ncRNAs (microRNAs, long ncRNAs, and circular RNAs) in the pathological processes of acute ischemic stroke–induced brain damage, as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Modulating role of circRNAs and microRNAs in neurobiological changes induced by drug exposure remains unclear. We examined alterations in some circRNAs and microRNAs in the striatum after morphine dependence and withdrawal and their associations with the changes in spatial working memory performance. Male Wistar rats were used in which 10 days morphine exposure induced dependence. Withdrawal effects were assessed 30 days after stopping morphine exposure. Spatial working memory was assessed using a Y maze test on days 1 and 10 of the drug exposure and 30 days after withdrawal. The gene and protein expression were assessed after dependence and withdrawal. The results revealed that 10 days morphine exposure impaired working memory, which partially reinstated after withdrawal. After 10 days morphine exposure, significant increases in Oprm1 gene and OPRM1 protein levels were detected, which persisted even after withdrawal. The expression of circOprm1 and miR-339-3p decreased in the morphine-dependent group, but they returned to normal levels after withdrawal. The expression of Tlr4 gene and TLR4 protein levels decreased after dependence. While Tlr4 mRNA levels returned to normal after withdrawal, TLR4 protein levels remained lower than the control group. In the morphine-dependent group, both Serpini1 and circSerpini expression significantly increased, but they restored after withdrawal. Expression of miR-181b-3p, miR-181b-5p, miR-181c-3p, and miR-181c-5p decreased after dependence, but they reinstated after withdrawal. It can be concluded that circOprm1 and circSerpini via regulating the OPRM1 and TLR4 expression in the striatum are associated with the neuroadaptation underlying spatial working memory after both morphine dependence and withdrawal. [ABSTRACT FROM AUTHOR]

Abstract The resistance of cancer cells to treatment significantly impedes the success of therapy, leading to the recurrence of various types of cancers. Understanding the specific mechanisms of therapy resistance may offer novel approaches for alleviating drug resistance in cancer. Recent research has shown a reciprocal relationship between circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification, and their interaction can affect the resistance and sensitivity of cancer therapy. This review aims to summarize the latest developments in the m6A modification of circRNAs and their importance in regulating therapy resistance in cancer. Furthermore, we explore their mutual interaction and exact mechanisms and provide insights into potential future approaches for reversing cancer resistance.

Circular RNAs (circRNAs) play important roles in many human diseases. However, their role in the development of severe sepsis, a condition that remains one of the main causes of death in intensive care units, has not yet been defined. In this study, we interrogated the molecular mechanisms of circRNAs in severe sepsis. We profiled the expression levels of 5,680 circRNAs in plasma extracted from blood samples of 9 severe sepsis cases or 9 controls (male, age 78 ± 7) using the Human circRNA Array. To enrich protein-coding genes hosting severe sepsis-related circRNAs, we conducted gene ontology and pathways analyses. Out of the identified 760 differentially expressed circRNAs, 404 were upregulated while 356 were downregulated (fold change [FC] ≥2 or ≤−2, and false discovery ratio

Yan Guo,1,* Jing-Jing Pan,2,* Wen Zhu,1 Mu-Zi Wang,3 Tian-Yu Liu,4 Xiao-Xin Wang,5 Qian-Qian Wu,1 Yi-Xin Cheng,1 Yi-Sen Qian,1 Xiao-Guang Zhou,1 Yang Yang1 1Department of Neonatology, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neonatology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Neonatology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, People’s Republic of China; 4Department of Neonatology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, People’s Republic of China; 5Department of Pediatrics, Shandong Tumor Hospital, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Guang Zhou; Yang Yang, Department of Neonatology, Children’s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Email gzzhouxg@163.com; yy860507@126.comObjective: This prospective study is to explore the role of specific circRNAs in predicting the development of bronchopulmonary dysplasia (BPD).Methods: From July 1, 2021 to December 1, 2021, peripheral blood samples were collected from 62 premature infants with gestational age (GA) ≤ 32 weeks on the 7th, 14th, and 28th day after birth. Then, on the 28th day, the included infants were divided into the BPD group and the non-BPD group according to the definition of BPD. Serum exosomal circRNAs from peripheral blood were identified, sequenced, and compared between the BPD and non-BPD groups at different time points. Specific differentially expressed circRNAs were further verified from another 42 enrolled premature infants (GA ≤ 32 weeks). The classical lung biological markers in serum were also measured simultaneously.Results: Hsa_circ_0001359 in serum exosomes showed continuous differential expression between the BPD group and the non-BPD group on the 7th, 14th, and 28th day. Compared with that, classical lung biological markers like IL-6, IL-33, KL-6, and ET-1 did not exhibit continuous differences. Moreover, the expression of hsa_circ_0001359 on day 7 had a higher predictive value in predicting BPD (area under curve:0.853, 95% CI:0.738– 0.968; adjusted odds ratio:6.033, 95% CI:2.373– 13.326). The calibration curve further showed the mean absolute error = 0.033, mean squared error = 0.00231, and quantile of absolute error = 0.058.Conclusion: Hsa_circ_0001359 in serum exosomes is a promising marker for predicting BPD in preterm infants with gestational age ≤ 32 weeks.Keywords: bronchopulmonary dysplasia, circular RNAs, high-throughput sequencing, preterm infants

Honggang Guo,1,* Yabin Cui,2,* Yanliang Bai,1 Fan Yan,1 Wenhui Zhang,1 Yuqing Chen,1,* Mingyue Shi1,* 1Department of Hematology, Zhengzhou University People’s Hospital and Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Hematology, Henan University People’s Hospital, Zhengzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuqing Chen; Mingyue Shi, Department of Hematology, Zhengzhou University People’s Hospital and Henan Provincial People’s Hospital, #7 Weiwu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86-18697321863 ; +86-17839931733, Email henanblood@sina.com; shimingyue16@gmail.comBackground: Relapsed/refractory acute myeloid leukemia (R/R-AML) has dismal prognosis due to chemotherapy resistance. Circular RNAs (circRNAs) have shown emerging roles in chemotherapy resistance in various cancers including hematologic malignancies. However, the potential roles of circRNAs in AML progression and drug resistance remain largely undetermined.Methods: In this study, circulating circRNAs expression profiles were analyzed among R/R-AML, de novo AML and healthy controls (HC) using a human circRNA Array. Bioinformatic analysis was carried out to explore the differentially expressed circRNAs (DE-circRNAs). GO, KEGG pathway analysis, along with circRNA-miRNA-mRNA network analysis, were conducted to identify the potential biological pathways involved in R/R-AML. Finally, the UALCAN database was used to assess the prognosis of different target DE-circRNAs-related mRNAs.Results: Forty-eight DE-circRNAs were upregulated, whereas twenty-seven DE-circRNAs were downregulated in R/R-AML samples. Up-regulated DE-circRNAs in R/R-AML samples were mainly enrichment in the biological processes and pathways of cell migration, microRNAs in cancers, Rap1 and Ras signaling pathways. Six DE-circRNAs were randomly selected to further explore their relationships with R/R-AML. GO and KEGG pathway analyses of the six candidate DE-circRNAs-related target mRNAs were mainly involved in the regulation of signal transduction and Ras signaling pathway. By overlapping our RNA-sequencing results of differentially expressed genes (DEGs) in R/R-AML samples with the candidate DE-circRNAs-predicted target mRNAs, we identified sixty-eight overlapping targeted mRNAs. Using UALCAN database analysis, we identified that AML patients with six upregulated DE-circRNA-related genes (ECE1, PI4K2A, SLC9A6, CCND3, PPP1R16B, and TRIM32) and one downregulated gene DE-circRNA-related genes (ARHGAP10) might have a poor prognosis.Conclusion: This study revealed the overall alterations of circRNAs in R/R-AML. DE-circRNAs and their related genes might be used as potential early, sensitive and stable biomarkers for AML diagnosis, R/R-AML monitoring, and even as novel treatment targets for R/R-AML.Keywords: Relapsed/refractory, acute myeloid leukemia, circular RNAs, biomarkers, prognosis

Abstract Background Circular RNAs (circRNAs) have been recognized as significant regulators of pulmonary hypertension (PH); however, the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown. Here, we identified co‐differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells (PASMCs), pulmonary microvascular endothelial cells (PMECs), and pericytes (PCs) under hypoxia. Methods Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types. Bioinformatic analysis was used to predict their putative biological function. Quantitative real‐time polymerase chain reaction, Cell Counting Kit‐8, and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1 (circPMS1) as well as its potential sponge mechanism in PASMCs, PMECs, and PCs. Results PASMCs, PMECs, and PCs exhibited 16, 99, and 31 differentially expressed circRNAs under hypoxia, respectively. CircPMS1 was upregulated in PASMCs, PMECs, and PCs under hypoxia and enhanced the proliferation of vascular cells. CircPMS1 may upregulate DEP domain containing 1 (DEPDC1) and RNA polymerase II subunit D expression by targeting microRNA‐432‐5p (miR‐432‐5p) in PASMCs, upregulate MAX interactor 1 (MXI1) expression by targeting miR‐433‐3p in PMECs, and upregulate zinc finger AN1‐type containing 5 (ZFAND5) expression by targeting miR‐3613‐5p in PCs. Conclusions Our results suggest that circPMS1 promotes cell proliferation through the miR‐432‐5p/DEPDC1 or miR‐432‐5p/POL2D axis in PASMCs, through the miR‐433‐3p/MXI1 axis in PMECs, and through the miR‐3613‐5p/ZFAND5 axis in PCs, which provides putative targets for the early diagnosis and treatment of PH.

Polycystic ovary syndrome (PCOS) is the most common condition affecting women of reproductive age globally. PCOS continues to be the largest contributing factor to female infertility despite significant progress in our knowledge of the molecular underpinnings and treatment of the condition. The fact that PCOS is a very diverse condition makes it one of the key reasons why we haven't been able to overcome it. Non-coding RNAs (ncRNAs) are implicated in the development of PCOS, according to growing evidence. However, it is unclear how the complex regulatory relationships between the many ncRNA types contribute to the growth of this malignancy. Competing endogenous RNA (ceRNA), a recently identified mechanism in the RNA world, suggests regulatory interactions between various RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), transcribed pseudogenes, and circular RNAs (circRNAs). Recent studies on PCOS have shown that dysregulation of multiple ceRNA networks (ceRNETs) between these ncRNAs plays crucial roles in developing the defining characteristics of PCOS development. And it is believed that such a finding may open a new door for a deeper comprehension of PCOS's unexplored facets. In addition, it may be able to provide fresh biomarkers and effective therapy targets for PCOS. This review will go over the body of information that exists about the primary roles of ceRNETs before highlighting the developing involvement of several newly found ceRNETs in a number of PCOS characteristics.

CircRNAs are a class of single-stranded RNAs characterized by covalently looped structures. Emerging advances have promoted our understanding of circRNA biogenesis, nuclear export, biological functions, and functional mechanisms. Roles of circRNAs in diverse diseases have been increasingly recognized in the past decade, with novel approaches in bioinformatics analysis and new strategies in modulating circRNA levels, which have made circRNAs the hot spot for therapeutic applications. Moreover, due to the intrinsic features of circRNAs such as high stability, conservation, and tissue-/stage-specific expression, circRNAs are believed to be promising prognostic and diagnostic markers for diseases. Aiming cardiovascular disease (CVD), one of the leading causes of mortality worldwide, we briefly summarize the current understanding of circRNAs, provide the recent progress in circRNA functions and functional mechanisms in CVD, and discuss the future perspectives both in circRNA research and therapeutics based on existing knowledge.

The resistance of cancer cells to treatment significantly impedes the success of therapy, leading to the recurrence of various types of cancers. Understanding the specific mechanisms of therapy resistance may offer novel approaches for alleviating drug resistance in cancer. Recent research has shown a reciprocal relationship between circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification, and their interaction can affect the resistance and sensitivity of cancer therapy. This review aims to summarize the latest developments in the m6A modification of circRNAs and their importance in regulating therapy resistance in cancer. Furthermore, we explore their mutual interaction and exact mechanisms and provide insights into potential future approaches for reversing cancer resistance. [ABSTRACT FROM AUTHOR]

The role of messenger RNA (mRNA) in biological systems is extremely versatile. However, it’s extremely short half-life poses a fundamental restriction on its application. Moreover, the translation efficiency of mRNA is also limited. On the contrary, circular RNAs, also known as circRNAs, are a common and stable form of RNA found in eukaryotic cells. These molecules are synthesized via back-splicing. Both synthetic circRNAs and certain endogenous circRNAs have the potential to encode proteins, hence suggesting the potential of circRNA as a gene expression machinery. Herein, we aim to summarize all engineering aspects that allow exogenous circular RNA (circRNA) to prolong the time that proteins are expressed from full-length RNA signals. This review presents a systematic engineering approach that have been devised to efficiently assemble circRNAs and evaluate several aspects that have an impact on protein production derived from. We have also reviewed how optimization of the key components of circRNAs, including the topology of vector, 5′ and 3′ untranslated sections, entrance site of the internal ribosome, and engineered aptamers could be efficiently impacting the translation machinery for molecular and metabolic reprogramming. Collectively, molecular and metabolic reprogramming present a novel way of regulating distinctive cellular features, for instance growth traits to neoplastic cells, and offer new possibilities for therapeutic inventions. [ABSTRACT FROM AUTHOR]

Objective Investigation of the expression and clinical significance of circular RNA hsa&lowbar;circ&lowbar; 0003922 in endometrioid carcinoma (EEC) . Methods Three EEC tissues and three normal endometrial tissues were selected for high-throughput molecular sequencing to identify specific circRNAs and related functional molecules. Additionally, 36 EEC patients were selected as the experimental group, while 36 patients with benign uterine lesions served as the control group. The differentially expressed hsa&lowbar;circ&lowbar;0003922 was chosen as the research target, and its expression in EEC tissues and the control group was detected using real-time fluorescence quantitative PCR (RT-qPCR) . The relationship between its expression level and clinical pathological features of EEC was analyzed. Furthermore, the miRNAs associated with hsa&lowbar;circ&lowbar;0003922 were predicted. The receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic value of hsa&lowbar;circ&lowbar;0003922 for EEC. Results The results of high-throughput molecular sequencing showed that there were 293 differentially expressed circRNAs in EEC tissues compared to the control group, including 115 upregulated and 178 downregulated circRNAs. RT-qPCR further revealed that the expression of hsa&lowbar;circ&lowbar;0003922 was significantly decreased in EEC tissues compared to the control group (P < 0.05) . The expression level of hsa&lowbar;circ&lowbar;0003922 was significantly negatively correlated with FIGO staging and histological grading of EEC (P < 0.05) . The area under the ROC curve (AUC) for hsa&lowbar;circ&lowbar;0003922 in distinguishing EEC patients from the control group was 0.7724 (P<0.05) . Conclusion The expression of hsa&lowbar;circ&lowbar;0003922 is associated with FIGO staging and histological grading of EEC, indicating its potential as a reference index for auxiliary diagnosis, prognosis evaluation, and as a potential molecular target for adjuvant therapy in EEC. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression. This study aimed to investigate the role and molecular mechanisms of circMYO1C in OA. CircMYO1C was upregulated in OA‐ and interleukin‐1β (IL‐1β)‐exposed chondrocytes. The results indicated that circMYO1C knockdown repressed the inflammatory factors (tumor necrosis factor alpha [TNF‐α], interleukin‐6 [IL‐6], interleukin‐8 [IL‐8], etc.) and apoptosis of chondrocytes following IL‐1β exposure. CircMYO1C was an N6‐methyladenosine (m6A)‐modified circRNA with m6A characteristics. High mobility group box 1 (HMGB1) was a target of circMYO1C. IL‐1β exposure increased the stability and half‐life (t1/2) of HMGB1 mRNA, while silencing circMYO1C reduced HMGB1 mRNA stability. Taken together, circMYO1C targets the m6A/HMGB1 axis to promote chondrocyte apoptosis and inflammation. The present study demonstrates that the circMYO1C/m6A/HMGB1 axis is essential for OA progression, highlighting a novel potential therapeutic target for clinical OA. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Despite the fact that the functional mechanisms of most circRNAs remain unknown, emerging evidence indicates that circRNAs could sponge microRNAs (miRNAs), bind to RNA binding proteins (RBP), and even be translated into protein. Recent research has demonstrated the crucial roles played by circRNAs in neuropsychiatric disorders. The medial prefrontal cortex (mPFC) is a crucial component of drug reward circuitry and exerts top-down control over cognitive functions. However, there is currently limited knowledge about the correlation between circRNAs and morphine-associated contextual memory in the mPFC. Here, we performed morphine-induced conditioned place preference (CPP) in mice and extracted mPFC tissue for RNA-sequencing. Our study represented the first attempt to identify differentially expressed circRNAs (DEcircRNAs) and mRNAs (DEmRNAs) in the mPFC after morphine-induced CPP. We identified 47 significantly up-regulated DEcircRNAs and 429 significantly up-regulated DEmRNAs, along with 74 significantly down-regulated DEcircRNAs and 391 significantly down-regulated DEmRNAs. Functional analysis revealed that both DEcircRNAs and DEmRNAs were closely associated with neuroplasticity. To further validate the DEcircRNAs, we conducted qRT-PCR, Sanger sequencing, and RNase R digestion assays. Additionally, using an integrated bioinformatics approach, we constructed ceRNA networks and identified critical circRNA/miRNA/mRNA axes that contributed to the development of morphine-associated contextual memory. In summary, our study provided novel insights into the role of circRNAs in drug-related memory, specifically from the perspective of ceRNAs. [ABSTRACT FROM AUTHOR]

Circular RNA (circRNA) vaccines have attracted increasing attention due to their stable closed-loop structures and persistent protein expression ability. During the synthesis process, nicked circRNAs with similar molecular weights to those of circRNAs are generated. Analytical techniques based on differences in molecular weight, such as capillary electrophoresis, struggle to distinguish between circRNAs and nicked circRNAs. The characteristic degradation products of circRNAs and their biological activities remain unclear. Therefore, developing methods to identify target circRNAs and non-target components and investigating degradation patterns will be beneficial to gaining an in-depth understanding of the properties and quality control of circRNAs vaccines. The reversed-phase HPLC (RP-HPLC) method was established for identification of target circRNAs, product-related substances, and impurities. Subsequently, we investigated the degradation patterns of circRNAs under thermal acceleration conditions and performed biological analysis of degradation products and linear precursors. Here, RP-HPLC method effectively identified circRNAs and nicked circRNAs. With thermal acceleration, circRNAs exhibited a "circular→nicked circRNAs→degradation products" degradation pattern. Biological analysis revealed that the immunogenicity of degradation products significantly decreased, whereas linear precursors did not possess immunogenicity. Thus, our established RP-HPLC method can be used for purity analysis of circRNA vaccines, which contributes to the quality control of circRNA vaccines and promoting the development of circRNA technology. [ABSTRACT FROM AUTHOR]

In recent years, burgeoning research has underscored the pivotal role of noncoding RNA in orchestrating the growth, development, and pathogenesis of various diseases across organisms. However, despite these advances, our understanding of the specific contributions of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) to lens development remains notably limited. Clarifying the intricate gene regulatory networks is imperative for unraveling the molecular underpinnings of lens-related disorders. In this study, we aimed to address this gap by conducting a comprehensive analysis of the expression profiles of messenger RNAs (mRNAs), lncRNAs, and circRNAs at critical developmental time points of the mouse lens, encompassing both embryonic (E10.5, E12.5, and E16.5) and postnatal stages (P0.5, P10.5, and P60). Leveraging RNA-sequencing technology, we identified key transcripts pivotal to lens development. Our analysis revealed differentially expressed (DE) mRNAs, lncRNAs, and circRNAs across various developmental stages. Particularly noteworthy, there were 1831 co-differentially expressed (CO-DE) mRNAs, 150 CO-DE lncRNAs, and 13 CO-DE circRNAs identified during embryonic stages. Gene Ontology (GO) enrichment analysis unveiled associations primarily related to lens development, DNA conformational changes, and angiogenesis among DE mRNAs and lncRNAs. Furthermore, employing protein-protein interaction networks, mRNA-lncRNA co-expression networks, and circRNA-microRNA-mRNA networks, we predicted candidate key molecules implicated in lens development. Our findings underscore the pivotal roles of lncRNAs and circRNAs in this process, offering fresh insights into the pathogenesis of lens-related disorders and paving the way for future exploration in this field. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) play an important role in the occurrence and development of diseases. However, the role of circRNAs in male smokers with chronic obstructive pulmonary disease (COPD) remains unclear. Methods: Stable COPD patients and healthy controls were recruited. Peripheral blood mononuclear cells (PBMCs) were extracted. After high-throughput RNA sequencing (RNA-Seq) of PBMCs, a bioinformatics method was used to analyse differentially expressed (DE) circRNAs (DEcircRNAs) and mRNAs (DEmRNAs). Results: Total of 114 DEcircRNAs and 58 DEmRNAs were identified. Functional enrichment analysis showed that processes related to COPD include the regulation of interleukin (IL)-18, IL-5 and the NLRP3 inflammasome; differentiation of T helper type 1 (Th1), Th2, and Th17 cells, and the AMPK, Wnt, JAK-STAT, and PI3K-Akt signalling pathways. In the protein-protein interaction (PPI) network, the core genes were MYO16, MYL4, SCN4A, NRCAM, HMCN1, MYOM2, and IQSEC3. Small-molecule prediction results revealed potential drugs for the COPD treatment. Additionally, the circRNAmiRNA-mRNA competitive endogenous RNA (ceRNA) regulatory network was constructed. Conclusion: This study identified a set of dysregulated circRNAs and mRNAs and revealed potentially important genes, pathways, new small-molecule drugs and ceRNA regulatory networks in male smokers with COPD. These circRNAs might be prospective biomarkers or potential molecular targets of the ceRNA mechanism for COPD. [ABSTRACT FROM AUTHOR]

T lymphocytes play a critical role in antitumor immunity, but their exhaustion poses a significant challenge for immune evasion by malignant cells. Circular RNAs (circRNAs), characterized by their covalently closed looped structure, have emerged as pivotal regulators within the neoplastic landscape. Recent studies have highlighted their multifaceted roles in cellular processes, including gene expression modulation and protein function regulation, which are often disrupted in cancer. In this review, we systematically explore the intricate interplay between circRNAs and T cell modulation within the tumor microenvironment. By dissecting the regulatory mechanisms through which circRNAs impact T cell exhaustion, we aim to uncover pathways crucial for immune evasion and T cell dysfunction. These insights can inform innovative immunotherapeutic strategies targeting circRNA-mediated molecular pathways. Additionally, we discuss the translational potential of circRNAs as biomarkers for therapeutic response prediction and as intervention targets. Our comprehensive analysis aims to enhance the understanding of immune evasion dynamics in the tumor microenvironment by facilitating the development of precision immunotherapy. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have emerged as pivotal regulators of gene expression with diverse roles in various biological processes. In recent years, research into circRNAs' involvement in bone biology has gained significant attention, unveiling their potential as novel regulators and biomarkers in bone-related disorders and diseases. CircRNAs, characterized by their closed-loop structure, exhibit stability and resistance to degradation, underscoring their functional significance. In bone tissue, circRNAs are involved in critical processes such as osteogenic differentiation, osteoclastogenesis, and bone remodeling through intricate molecular mechanisms including microRNA regulation. Dysregulated circRNAs are associated with various bone disorders, suggesting their potential as diagnostic and prognostic biomarkers. The therapeutic targeting of these circRNAs holds promise for addressing bone-related conditions, offering new perspectives for precision medicine. Thus, circRNAs constitute integral components of bone regulatory networks, impacting both physiological bone homeostasis and pathological conditions. This review provides a comprehensive overview of circRNAs in bone biology, emphasizing their regulatory mechanisms, functional implications, and therapeutic potential. [ABSTRACT FROM AUTHOR]

Cardiac remodelling involves structural, cellular and molecular alterations in the heart after injury, resulting in progressive loss of heart function and ultimately leading to heart failure. Circular RNAs (circRNAs) are a recently rediscovered class of non‐coding RNAs that play regulatory roles in the pathogenesis of cardiovascular diseases, including heart failure. Thus, a more comprehensive understanding of the role of circRNAs in the processes governing cardiac remodelling may set the ground for the development of circRNA‐based diagnostic and therapeutic strategies. In this review, the current knowledge about circRNA origin, conservation, characteristics and function is summarized. Bioinformatics and wet‐lab methods used in circRNA research are discussed. The regulatory function of circRNAs in cardiac remodelling mechanisms such as cell death, cardiomyocyte hypertrophy, inflammation, fibrosis and metabolism is highlighted. Finally, key challenges and opportunities in circRNA research are discussed, and orientations for future work to address the pharmacological potential of circRNAs in heart failure are proposed. [ABSTRACT FROM AUTHOR]

Cardiovascular disease, specifically heart failure (HF), remains a significant concern in the realm of healthcare, necessitating the development of new treatments and biomarkers. The RNA family consists of various subgroups, including microRNAs, PIWI-interacting RNAs (piRAN) and long non-coding RNAs, which have shown potential in advancing personalized healthcare for HF patients. Recent research suggests that circular RNAs, a lesser-known subgroup of RNAs, may offer a novel set of targets and biomarkers for HF. This review will discuss the biogenesis of circular RNAs, their unique characteristics relevant to HF, their role in heart function, and their potential use as biomarkers in the bloodstream. Furthermore, future research directions in this field will be outlined. The stability of exosomal circRNAs makes them suitable as biomarkers, pathogenic regulators, and potential treatments for cardiovascular diseases such as atherosclerosis, acute coronary syndrome, ischemia/reperfusion injury, HF, and peripheral artery disease. Herein, we summarized the role of circular RNAs and their exosomal forms in HF diseases. [ABSTRACT FROM AUTHOR]

This document provides an overview of research studies on the role of RNA biology in endocrine-related cancers. It highlights the impact of RNA on tumor behavior and heterogeneity, focusing on processes like alternative splicing and noncoding RNA regulation. The studies suggest that aberrant RNA signatures can be used as diagnostic and prognostic biomarkers for these cancers, and ongoing research is uncovering potential therapeutic targets. The document emphasizes the need for further research in this field to improve the management and treatment of endocrine-related malignancies. [Extracted from the article]

Epidemiological evidence indicates exposure to glyphosate-based herbicides (GBHs) increases the risk for autism spectrum disorder (ASD). The gut microbiota has been found to influence ASD behaviours through the microbiota-gut-brain axis. However, the underlying links between early life GBH exposure and ASD-like phenotypes through the microbiota-gut-brain axis remain unclear. Therefore, we exposed mice to low-dose GBH (0.10, 0.25, 0.50, and 1.00 %) and determined the effects on ASD-like behaviours. Furthermore, three kinds of omics (gut microbiomics, metabolomics, and transcriptomics) were conducted to investigate the effects of GBH exposure on gut microbiota, gut metabolites, and circular RNAs (circRNAs) in the prefrontal cortex (PFC) using a cross-generational mouse model. Behavioural analyses suggested social impairment and repetitive/stereotypic behaviours in the GBH-exposed offspring. Furthermore, maternal exposure to glyphosate significantly altered the ASD-associated gut microbiota of offspring, and ASD-associated gut metabolites were identified. Specifically, we found that alterations in the gut microenvironment may contribute to changes in gut permeability and the blood-brain barrier, which are related to changes in the levels of circRNAs in the PFC. Our results suggest a potential effect of circRNAs through the disruption of the gut-brain interaction, which is an important factor in the pathogenesis of ASD in offspring induced by maternal exposure to GBH.

Abstract Circular RNAs (circRNAs) are a unique class of RNA molecules formed through back‐splicing rather than linear splicing. As an emerging field in molecular biology, circRNAs have garnered significant attention due to their distinct structure and potential functional implications. A comprehensive understanding of circRNAs’ functions and potential clinical applications remains elusive despite accumulating evidence of their involvement in disease pathogenesis. Recent research highlights their significant roles in various human diseases, but comprehensive reviews on their functions and applications remain scarce. This review provides an in‐depth examination of circRNAs, focusing first on their involvement in non‐neoplastic diseases such as respiratory, endocrine, metabolic, musculoskeletal, cardiovascular, and renal disorders. We then explore their roles in tumors, with particular emphasis on exosomal circular RNAs, which are crucial for cancer initiation, progression, and resistance to treatment. By detailing their biogenesis, functions, and impact on disease mechanisms, this review underscores the potential of circRNAs as diagnostic biomarkers and therapeutic targets. The review not only enhances our understanding of circRNAs’ roles in specific diseases and tumor types but also highlights their potential as novel diagnostic and therapeutic tools, thereby paving the way for future clinical investigations and potential therapeutic interventions.

Lingling Yuan,1 Ting Wang,1 Jinsheng Duan,2 Jing Zhou,1 Na Li,1 Guizhi Li,1 Hong Zhou1 1Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050004, People’s Republic of China; 2Department of Cardiology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050004, People’s Republic of ChinaCorrespondence: Hong Zhou, Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Tel +86-15130119625, Email zhoubs2013@hebmu.edu.cn; zhoubs2013@163.comIntroduction: Cardiac fibrosis is one of the important causes of heart failure and death in diabetic cardiomyopathy (DCM) patients. Circular RNAs (circRNAs) are covalently closed RNA molecules in eukaryotes and have high stability. Their role in myocardial fibrosis with diabetic cardiomyopathy (DCM) remain to be fully elucidated. This study aimed to understand the expression profiles of circRNAs in myocardial fibrosis with DCM, exploring the possible biomarkers and therapeutic targets for DCM.Methods: At 21 weeks of age, db/db mice established the type 2 DCM model measured by echocardiography, and the cardiac tissue was extracted for Hematoxylin–eosin, Masson’s trichrome staining, and transmission electron microscopy. Subsequently, the expression profile of circRNAs in myocardial fibrosis of db/db mice was constructed using microarray hybridization and verified by real‐time quantitative polymerase chain reaction. A circRNA–microRNA–messenger RNA coexpression network was constructed, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were done.Results: Compared with normal control mice, db/db mice had 77 upregulated circRNAs and 135 downregulated circRNAs in their chromosomes (fold change ≥ 1.5, P ≤ 0.05). Moreover, the enrichment analysis of circRNA host genes showed that these differentially expressed circRNAs were mainly involved in mitogen-activated protein kinase signaling pathways. CircPHF20L1, circCLASP1, and circSLC8A1 were the key circRNAs. Moreover, circCLASP1/miR-182-5p/Wnt7a, circSLC8A1/miR-29b-1-5p/Col12a1, and most especially circPHF20L1/miR-29a-3p/Col6a2 might be three novel axes in the development of myocardial fibrosis in DCM.Conclusion: The findings will provide some novel circRNAs and molecular pathways for the prevention or clinical treatment of DCM through intervention with specific circRNAs.Keywords: Circular RNAs, expression profile, diabetic cardiomyopathy, cardiac fibrosis, bioinformatic analysis

Abstract Background Circular RNAs (circRNAs) are a novel kind of non-coding RNAs proved to play crucial roles in the development of multiple diabetic complications. However, their expression and function in diabetes mellitus (DM)-impaired salivary glands are unknown. Results By using microarray technology, 663 upregulated and 999 downregulated circRNAs companied with 813 upregulated and 525 downregulated mRNAs were identified in the parotid glands (PGs) of type2 DM mice under a 2-fold change and P