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Circular RNAs (circRNAs) are unique noncoding RNAs that have a closed and stable loop structure generated through backsplicing. Due to their conservation, stability and tissue specificity, circRNAs can potentially be used as diagnostic indicators and therapeutic targets for certain tumors. Many studies have shown that circRNAs can act as microRNA (miRNA) sponges, and engage in interactions with proteins and translation templates to regulate gene expression and signal transduction, thereby participating in the occurrence and development of a variety of malignant tumors. Immunotherapy has revolutionized the treatment of cancer. Early researches have indicated that circRNAs are involved in regulating tumor immune microenvironment and antitumor immunity. CircRNAs may have the potential to be important targets for increasing sensitivity to immunotherapy and expanding the population of patients who benefit from cancer immunotherapy. However, few studies have investigated the correlation between circRNAs and tumor immunity. In this review, we summarize the current researches on circRNAs involved in antitumor immune regulation through different mechanisms and their potential value in increasing immunotherapy efficacy with the goal of providing new targets for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are cardinal players in numerous physiological and pathological processes. CircRNAs play dual roles as tumor suppressors and oncogenes in different oncological contexts, including hepatocellular carcinoma (HCC). Their roles significantly impact the disease at all stages, including initiation, development, progression, invasion, and metastasis, in addition to the response to treatment. In this review, we discuss the biogenesis and regulatory functional roles of circRNAs, as well as circRNA–protein–mRNA ternary complex formation, elucidating the intricate pathways tuned by circRNAs to modulate gene expression and cellular processes through a comprehensive literature search, in silico search, and bioinformatics analysis. With a particular focus on the interplay between circRNAs, epigenetics, and HCC pathology, the article sets the stage for further exploration of circRNAs as novel investigational theranostic agents in the dynamic realm of HCC. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have gained significant attention in recent years. This bibliometric analysis aimed to provide insights into the current state and future trends of global circRNA research. The scientific output on circRNAs from 2010 to 2022 was retrieved from the Web of Science Core Collection with circRNA-related terms as the subjects. Key bibliometric indicators were calculated and evaluated using CiteSpace. A total of 7385 studies on circRNAs were identified. The output and citation number have increased rapidly after 2015. China, the USA, and Germany were top three publishing countries. Currently, circCDR1as, circHIPK3, circPVT1, circSHPRH, and circZNF609 are the most studied circRNAs; and all are related to cancer. The theme of research have shifted from transcript, exon circularization and miRNA sponge topics to the transcriptome, tumor suppressor, and biomarkers, indicating that research interests have evolved from basic to applied research. CircRNAs will continue to be a highly active research area in the near future. From the current understanding of circRNA characterization and regulatory mechanisms as miRNA sponges in cancer, future directions may examine potential diagnostic and therapeutic roles of circRNAs in cancers or the function and mechanism of circRNAs in other diseases. [ABSTRACT FROM AUTHOR]

Astrocytes are key targets for treating cerebral ischemia in the central nervous system. Non-coding RNAs (ncRNAs) participate in the pathological processes of astrocytes in cerebral ischemia. Recent reports suggest that ncRNAs ameliorate the outcome of cerebral ischemia by mediating astrocytes' inflammatory reaction, oxidative stress, excitotoxicity, autophagy, and apoptosis. Reconstructing cellular systems might offer a promising strategy for treating cerebral ischemia. This review briefly discusses the potential of ncRNAs as drug targets and explores the molecular regulatory mechanisms through which ncRNAs target astrocytes in cerebral ischemia. It provides an overview of the current research, discusses ncRNAs' implications as clinical markers for cerebral ischemia, and anticipates that ongoing research on ncRNAs may contribute to novel therapeutic approaches for treating this condition. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) have been implicated in the development and progression of gastric cancer (GC). However, it remains unclear whether dysregulated circRNA affects immune escape and the efficacy of immunotherapy in GC. Our aim is to investigate the molecular mechanism of circRNA affecting GC immunotherapy and identify effective molecular therapeutic targets. Methods: The differential expression profile of circRNAs was established through circRNA sequencing, comparing three paired GC tissues with their adjacent non-cancerous gastric tissues. The expression level of circRHBDD1 in GC tissues was then assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological characteristics of circRHBDD1 were verified through a series of experiments, including agarose gel electrophoresis assays, RNase R treatment, and actinomycin D experiments. The prognostic value of circRHBDD1 in GC was evaluated by conducting both univariate and multivariate survival analyses. Furthermore, loss- and gain-of-function approaches were utilized to investigate the impact of circRHBDD1 on GC immune escape. RNA-sequencing, immunoprecipitation, flow cytometry, and methylated RNA immunoprecipitation (meRIP) analysis were performed to elucidate the underlying molecular mechanisms. Results: We discovered that circRHBDD1 exhibited remarkably high expression levels in GC tissues and cell lines. Notably, the high expression of circRHBDD1 was significantly correlated with poor overall survival and disease-free survival among GC patients. Both in vitro and in vivo experiments revealed that circRHBDD1 upregulated the expression of PD-L1 and impeded the infiltration of CD8+ T cells. Further, we found that circRHBDD1 binds to IGF2BP2, disrupting the interaction between E3 ligase TRIM25 and IGF2BP2, and ultimately inhibiting IGF2BP2 ubiquitination and degradation. Intriguingly, IGF2BP2 enhances PD-L1 mRNA stability through m6A modification. Additionally, we developed Poly (lactide-co-glycolic acid) (PLGA)-Polyethylene glycol (PEG)-based nanoparticles loaded with circRHBDD1 siRNA. In vivo experiments validated that the combination of PLGA-PEG(si-circRHBDD1) and anti-PD-1 offers a safe and efficacious nano-drug regimen for cancer immunotherapy. Conclusion: Our results demonstrated that circRHBDD1 promoted GC immune escape by upregulating the expression of PD-L1 and reprogramming T cell-mediated immune response. Inhibition of circRHBDD1 expression could potentially enhance the response of GC patients to immunotherapy, thus improving treatment outcomes. Additionally, the development of a nanodrug delivery system provides a feasible approach for future clinical applications. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) possess unique biological properties and distribution characteristics that enable a variety of biological functions. N6-methyladenosine (m6A), a prevalent epigenetic modification in organisms, is regulated by factors including methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers). These factors play critical roles in various pathophysiological processes. There is growing evidence that m6A modifications are common within circRNAs, affecting their synthesis, translation, translocation, degradation, and stability. Additionally, circRNAs regulate biological processes that influence m6A modifications. This review explores the metabolism and functions of m6A modifications and circRNAs, their interactions, and their specific regulatory mechanisms in different tumors, offering insights into m6A-circRNA interaction in cancer. [ABSTRACT FROM AUTHOR]

AbstractThe gut microbiota features an abundance of diverse microorganisms and represents an important component of human physiology and metabolic homeostasis, indicating their roles in a wide array of physiological and pathological processes in the host. Maintaining balance in the gut microbiota is critical for normal functionality as microbial dysbiosis can lead to the occurrence and development of diseases through various mechanisms. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are non-coding RNAs that perform important regulatory functions for many processes. Furthermore, the gut microbiota and lncRNAs/circRNAs are known to interact in a range of both physiological and pathological activities. In this article, we review existing research relevant to the interaction between the gut microbiota and lncRNAs/circRNAs and investigate the role of their crosstalk in the pathogenesis of different diseases. Studies have shown that, the gut microbiota can target lncRNAs ENO1-IT1, BFAL1, and LINC00152 to regulate colorectal cancer development via various signaling pathways. In addition, the gut microbiota can influence mental diseases and lung tumor metastasis by modulating circRNAs such as circNF1-419, circ_0001239, circHIPK2 and mmu_circ_0000730. These findings provide a theoretical basis for disease prevention and treatment and suggest that gut microbiota-lncRNA/circRNA crosstalk has high clinical value. [ABSTRACT FROM AUTHOR]

Circular RNA (circRNA) is a type of non-coding RNA with multiple biological functions. Whole circRNA genomes in plants have been identified, and circRNAs have been demonstrated to be widely present and highly expressed in various plant tissues and organs. CircRNAs are highly stable and conserved in plants, and exhibit tissue specificity and developmental stage specificity. CircRNAs often interact with other biomolecules, such as miRNAs and proteins, thereby regulating gene expression, interfering with gene function, and affecting plant growth and development or response to environmental stress. CircRNAs are less studied in plants than in animals, and their regulatory mechanisms of biogenesis and molecular functions are not fully understood. A variety of circRNAs in plants are involved in regulating growth and development and responding to environmental stress. This review focuses on the biogenesis and regulatory mechanisms of circRNAs, as well as their biological functions during growth, development, and stress responses in plants, including a discussion of plant circRNA research prospects. Understanding the generation and regulatory mechanisms of circRNAs is a challenging but important topic in the field of circRNAs in plants, as it can provide insights into plant life activities and their response mechanisms to biotic or abiotic stresses as well as new strategies for plant molecular breeding and pest control. [ABSTRACT FROM AUTHOR]

Exosomes, as pivotal entities within the tumor microenvironment, orchestrate intercellular communication through the transfer of diverse molecules, among which non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and circRNAs play a crucial role. These ncRNAs, endowed with regulatory functions, are selectively incorporated into exosomes. Emerging evidence underscores the significance of exosomal ncRNAs in modulating key oncogenic processes in thyroid cancer (TC), including proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunoediting. The unique composition of exosomes shields their cargo from enzymatic and chemical degradation, ensuring their integrity and facilitating their specific expression in plasma. This positions exosomal ncRNAs as promising candidates for novel diagnostic and prognostic biomarkers in TC. Moreover, the potential of exosomes in the therapeutic landscape of TC is increasingly recognized. This review aims to elucidate the intricate relationship between exosomal ncRNAs and TC, fostering a deeper comprehension of their mechanistic involvement. By doing so, it endeavors to propel forward the exploration of exosomal ncRNAs in TC, ultimately paving the way for innovative diagnostic and therapeutic strategies predicated on exosomes and their ncRNA content. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is one of the most prevalent and conserved RNA modifications. It controls several biological processes, including the biogenesis and function of circular RNAs (circRNAs), which are a class of covalently closed-single stranded RNAs. Several studies have revealed that proteotoxic stress response induction could be a relevant anticancer therapy in Acute Myeloid Leukemia (AML). Furthermore, a strong molecular interaction between the m6A mRNA modification factors and the suppression of the proteotoxic stress response has emerged. Since the proteasome inhibition leading to the imbalance in protein homeostasis is strictly linked to the stress response induction, we investigated the role of Bortezomib (Btz) on m6A regulation and in particular its impact on the modulation of m6A-modified circRNAs expression. Here, we show that treating AML cells with Btz downregulated the expression of the m6A regulator WTAP at translational level, mainly because of increased oxidative stress. Indeed, Btz treatment promoted oxidative stress, with ROS generation and HMOX-1 activation and administration of the reducing agent N-acetylcysteine restored WTAP expression. Additionally, we identified m6A-modified circRNAs modulated by Btz treatment, including circHIPK3, which is implicated in protein folding and oxidative stress regulation. These results highlight the intricate molecular networks involved in oxidative and ER stress induction in AML cells following proteotoxic stress response, laying the groundwork for future therapeutic strategies targeting these pathways. [ABSTRACT FROM AUTHOR]

Within the intricate tapestry of molecular research, noncoding RNAs (ncRNAs) were historically overshadowed by a pervasive presumption of their inability to encode proteins or peptides. However, groundbreaking revelations have challenged this notion, unveiling select ncRNAs that surprisingly encode peptides specifically those nearing a succinct 100 amino acids. At the forefront of this epiphany stand lncRNAs and circRNAs, distinctively characterized by their embedded small open reading frames (sORFs). Increasing evidence has revealed different functions and mechanisms of peptides/proteins encoded by ncRNAs in cancer, including promotion or inhibition of cancer cell proliferation, cellular metabolism (glucose metabolism and lipid metabolism), and promotion or concerted metastasis of cancer cells. The discoveries not only accentuate the depth of ncRNA functionality but also open novel avenues for oncological research and therapeutic innovations. The main difficulties in the study of these ncRNA-derived peptides hinge crucially on precise peptide detection and sORFs identification. Here, we illuminate cutting-edge methodologies, essential instrumentation, and dedicated databases tailored for unearthing sORFs and peptides. In addition, we also conclude the potential of clinical applications in cancer therapy. [ABSTRACT FROM AUTHOR]

Cervical Cancer (CC) is one of the most prevalent neoplasms among women, considered the leading cause of gynecological death worldwide, and the fourth most common type of cancer. Regional metastasis is closely related to the low effectiveness of treatment, and validating biomarkers can optimize accuracy in diagnosis and prognosis. Among the potential biomarkers associated with disease metastasis are circular RNAs (circRNAs), whose altered expression has been linked to CC progression. In this context, this systematic review aims to compile information on the clinical-pathological significance and describe the biological function of circRNAs. Inclusion and exclusion criteria were used to include relevant literature, followed by in silico analysis. Additionally, we employed the UALCAN tools to search for host genes of circRNAs and expression data, miRTargetLink 2.0 to predict interactions of microRNA target genes and the Cytoscape software to predict possible interactions of microRNA target genes. According to the research, most circRNAs were found to be overexpressed and described as regulators of processes such as invasion, cell proliferation, apoptosis and migration. They were also implicated in clinical significance, including metastasis, TNM staging and microRNA interactions. CircRNAs may participate in critical processes in tumorigenesis; therefore, understanding the underlying molecular mechanisms of gene regulation in CC can contribute to the accuracy of diagnosis, prognosis and therapy. [ABSTRACT FROM AUTHOR]

Eggshell color plays important biological roles and attracts the attention of both egg retailers and researchers. However, whether non-coding RNAs are involved in pigment deposition among different eggshell colors remains unknown. In this study, RNA sequencing was used to analyse the uterine gland transcriptome (CircRNA and miRNA) of Changshun chicken blue-shell hens producing four different eggshell color eggs including dark blue PK(DB) and light blue (LB), dark brown and greenish (between blue and pink, DP) and pink (p). We found that miR-192-x, targeting SLC16a7, was expressed in DB, DP, and LB groups compared with the PK group, which indicates that miR-192-x may play a role in the blue eggshell color. KEGG and GO analyses showed that the "metabolic pathways" with targeted genes such BLVRA and HMOX1 were detected in dark and light blue color eggshell chickens, which confirms the different ratios of biliverdin and HO-1 involved in the deposition of blue color. As annotated by connectivity analysis, RASGRF1 and RASGRF2, belonging to the RASGRF family, are involved in the Ras signaling pathway, which plays an important role in cell growth, differentiation, metastasis and apoptosis. Our findings enrich the database of circRNA, miRNAs and genes for chicken uterine tissue, which will be useful in accelerating molecular selection for blue eggshell color layers. [ABSTRACT FROM AUTHOR]

m6A methylation, a ubiquitous modification on circRNAs, exerts a profound influence on RNA function, intracellular behavior, and diverse biological processes, including disease development. While prediction algorithms exist for mRNA m6A modifications, a critical gap remains in the prediction of circRNA m6A modifications. Therefore, accurate identification and prediction of m6A sites are imperative for understanding RNA function and regulation. This study presents a novel hybrid model combining a convolutional neural network (CNN) and a bidirectional long short-term memory network (BiLSTM) for precise m6A methylation site prediction in circular RNAs (circRNAs) based on data from HEK293 cells. This model exploits the synergy between CNN's ability to extract intricate sequence features and BiLSTM's strength in capturing long-range dependencies. Furthermore, the integrated attention mechanism empowers the model to pinpoint critical biological information for studying circRNA m6A methylation. Our model, exhibiting over 78% prediction accuracy on independent datasets, offers not only a valuable tool for scientific research but also a strong foundation for future biomedical applications. This work not only furthers our understanding of gene expression regulation but also opens new avenues for the exploration of circRNA methylation in biological research. [ABSTRACT FROM AUTHOR]

Cancer has been one of the most problematic health issues globally. Typically, all cancers share a common characteristic or cancer hallmark, such as sustaining cell proliferation, evading growth suppressors, and enabling replicative immortality. Indeed, cell cycle regulation in cancer is often found to be dysregulated, leading to an increase in aggressiveness. These dysregulations are partly due to the aberrant cellular signaling pathway. In recent years, circular RNAs (circRNAs) have been widely studied and classified as one of the regulators in various cancers. Numerous studies have reported that circRNAs antagonize or promote cancer progression through the modulation of cell cycle regulators or their associated signaling pathways, directly or indirectly. Mostly, circRNAs are known to act as microRNA (miRNA) sponges. However, they also hold additional mechanisms for regulating cellular activity, including protein binding, RNA-binding protein (RBP) recruitment, and protein translation. This review will discuss the current knowledge of how circRNAs regulate cell cycle-related proteins through the abovementioned mechanisms in different cancers. [ABSTRACT FROM AUTHOR]

Increasing research has shown that the abnormal expression of microRNA (miRNA) is associated with many complex diseases. However, biological experiments have many limitations in identifying the potential disease-miRNA associations. Therefore, we developed a computational model of Three-Layer Heterogeneous Network based on the Integration of CircRNA information for MiRNA-Disease Association prediction (TLHNICMDA). In the model, a disease-miRNA-circRNA heterogeneous network is built by known disease-miRNA associations, known miRNA-circRNA interactions, disease similarity, miRNA similarity, and circRNA similarity. Then, the potential disease-miRNA associations are identified by an update algorithm based on the global network. Finally, based on global and local leave-one-out cross validation (LOOCV), the values of AUCs in TLHNICMDA are 0.8795 and 0.7774. Moreover, the mean and standard deviation of AUC in 5-fold cross-validations is 0.8777 +/−0.0010. Especially, the two types of case studies illustrated the usefulness of TLHNICMDA in predicting disease-miRNA interactions. [ABSTRACT FROM AUTHOR]

This manuscript summarizes information on the diverse range of RNA molecules and their role as competing endogenous RNAs (ceRNAs). Moreover, it provides an overview of ceRNA regulatory networks and their applications in ruminant biology. Knowledge of co-expression networks has increased with microarrays, RNA-seq, and scRNA-seq characterizing molecular mediators across various biological scales, using sequences from numerous blood and tissue samples. By synthesizing existing knowledge, this study summarizes interactions between coding and non-coding RNAs through microRNA response elements (MREs), elucidating large-scale regulatory networks throughout the transcriptome that influence the expression and activities of various ceRNAs. Identification of non-coding RNAs with important regulatory functions will revolutionize understanding of RNA biology, shifting from an mRNA-centric model to a complex network of RNA crosstalk. The ceRNA networks offer a more comprehensive and arguably more realistic perspective compared to protein–protein interaction (PPI) networks and weighted gene co-expression networks (WGCN). These ceRNA regulatory networks can describe potential molecular regulatory mechanisms related to functional and economically important traits in ruminants, plus contribute to disease and pathology research, by elucidating pathogenesis and potential drug effects in disease and cancer models. Furthermore, they can provide insights into farm animal biology, e.g., reproductive traits in goats and sheep, regulation of fat metabolism in beef cattle, heat stress responses, and lactation regulation in dairy cattle, fertility and muscle characteristics in buffalo, and resistance to high-salt and water-deprivation conditions in camels. In conclusion, ceRNA and associated regulatory networks should promote a new understanding of molecular mechanisms and identify candidate genes and metabolic-signaling pathways in ruminants. [ABSTRACT FROM AUTHOR]

Abstract Circular RNAs (circRNAs) are unique noncoding RNAs that have a closed and stable loop structure generated through backsplicing. Due to their conservation, stability and tissue specificity, circRNAs can potentially be used as diagnostic indicators and therapeutic targets for certain tumors. Many studies have shown that circRNAs can act as microRNA (miRNA) sponges, and engage in interactions with proteins and translation templates to regulate gene expression and signal transduction, thereby participating in the occurrence and development of a variety of malignant tumors. Immunotherapy has revolutionized the treatment of cancer. Early researches have indicated that circRNAs are involved in regulating tumor immune microenvironment and antitumor immunity. CircRNAs may have the potential to be important targets for increasing sensitivity to immunotherapy and expanding the population of patients who benefit from cancer immunotherapy. However, few studies have investigated the correlation between circRNAs and tumor immunity. In this review, we summarize the current researches on circRNAs involved in antitumor immune regulation through different mechanisms and their potential value in increasing immunotherapy efficacy with the goal of providing new targets for cancer immunotherapy.

Abstract Protein-encoding circular RNAs (circRNAs) are newly identified RNA molecules characterized by intense interaction with translating ribosome. Emerging evidence has implicated physiological and pathological significance of these non-canonical RNAs, yet a large body of them remains unidentified. Due to limited tools at hand, we developed CircProPlus, an automated computational pipeline for de novo detection of translated circRNAs. In comparison to previously established CircPro, CircProPlus adjusts the overall workflow and integrates more robust implements for achieving easier accessibility, higher flexibility and productivity. In present study, we tested the performance of CircProPlus when using different circRNA-detecting implements (i.e., CIRI2, CirComPara2) in the evaluation of coding ability of circRNAs. Results showed that CirComPara2, a state-of-the-art algorithm, consistently outperformed CIRI2 when coupled with CircProPlus in testing real data collected from different RNA libraries and species, which highlighted its potency in data mining of circRNAs with protein-coding potential.

Abstract Background Circular RNAs (circRNAs) have been implicated in the development and progression of gastric cancer (GC). However, it remains unclear whether dysregulated circRNA affects immune escape and the efficacy of immunotherapy in GC. Our aim is to investigate the molecular mechanism of circRNA affecting GC immunotherapy and identify effective molecular therapeutic targets. Methods The differential expression profile of circRNAs was established through circRNA sequencing, comparing three paired GC tissues with their adjacent non-cancerous gastric tissues. The expression level of circRHBDD1 in GC tissues was then assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological characteristics of circRHBDD1 were verified through a series of experiments, including agarose gel electrophoresis assays, RNase R treatment, and actinomycin D experiments. The prognostic value of circRHBDD1 in GC was evaluated by conducting both univariate and multivariate survival analyses. Furthermore, loss- and gain-of-function approaches were utilized to investigate the impact of circRHBDD1 on GC immune escape. RNA-sequencing, immunoprecipitation, flow cytometry, and methylated RNA immunoprecipitation (meRIP) analysis were performed to elucidate the underlying molecular mechanisms. Results We discovered that circRHBDD1 exhibited remarkably high expression levels in GC tissues and cell lines. Notably, the high expression of circRHBDD1 was significantly correlated with poor overall survival and disease-free survival among GC patients. Both in vitro and in vivo experiments revealed that circRHBDD1 upregulated the expression of PD-L1 and impeded the infiltration of CD8+ T cells. Further, we found that circRHBDD1 binds to IGF2BP2, disrupting the interaction between E3 ligase TRIM25 and IGF2BP2, and ultimately inhibiting IGF2BP2 ubiquitination and degradation. Intriguingly, IGF2BP2 enhances PD-L1 mRNA stability through m6A modification. Additionally, we developed Poly (lactide-co-glycolic acid) (PLGA)-Polyethylene glycol (PEG)-based nanoparticles loaded with circRHBDD1 siRNA. In vivo experiments validated that the combination of PLGA-PEG(si-circRHBDD1) and anti-PD-1 offers a safe and efficacious nano-drug regimen for cancer immunotherapy. Conclusion Our results demonstrated that circRHBDD1 promoted GC immune escape by upregulating the expression of PD-L1 and reprogramming T cell-mediated immune response. Inhibition of circRHBDD1 expression could potentially enhance the response of GC patients to immunotherapy, thus improving treatment outcomes. Additionally, the development of a nanodrug delivery system provides a feasible approach for future clinical applications.

Abstract Circular RNAs (circRNAs) possess unique biological properties and distribution characteristics that enable a variety of biological functions. N6-methyladenosine (m6A), a prevalent epigenetic modification in organisms, is regulated by factors including methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers). These factors play critical roles in various pathophysiological processes. There is growing evidence that m6A modifications are common within circRNAs, affecting their synthesis, translation, translocation, degradation, and stability. Additionally, circRNAs regulate biological processes that influence m6A modifications. This review explores the metabolism and functions of m6A modifications and circRNAs, their interactions, and their specific regulatory mechanisms in different tumors, offering insights into m6A-circRNA interaction in cancer.

Abstract Within the intricate tapestry of molecular research, noncoding RNAs (ncRNAs) were historically overshadowed by a pervasive presumption of their inability to encode proteins or peptides. However, groundbreaking revelations have challenged this notion, unveiling select ncRNAs that surprisingly encode peptides specifically those nearing a succinct 100 amino acids. At the forefront of this epiphany stand lncRNAs and circRNAs, distinctively characterized by their embedded small open reading frames (sORFs). Increasing evidence has revealed different functions and mechanisms of peptides/proteins encoded by ncRNAs in cancer, including promotion or inhibition of cancer cell proliferation, cellular metabolism (glucose metabolism and lipid metabolism), and promotion or concerted metastasis of cancer cells. The discoveries not only accentuate the depth of ncRNA functionality but also open novel avenues for oncological research and therapeutic innovations. The main difficulties in the study of these ncRNA-derived peptides hinge crucially on precise peptide detection and sORFs identification. Here, we illuminate cutting-edge methodologies, essential instrumentation, and dedicated databases tailored for unearthing sORFs and peptides. In addition, we also conclude the potential of clinical applications in cancer therapy.

The intricate molecular landscape of cancer pathogenesis continues to captivate researchers worldwide, with Circular RNAs (circRNAs) emerging as pivotal players in the dynamic regulation of biological functions. The study investigates the elusive link between circRNAs and the Transforming Growth Factor-β (TGF-β) signalling pathway, exploring their collective influence on cancer progression and metastasis. Our comprehensive investigation begins by profiling circRNA expression patterns in diverse cancer types, revealing a repertoire of circRNAs intricately linked to the TGF-β pathway. Through integrated bioinformatics analyses and functional experiments, we elucidate the specific circRNA-mRNA interactions that modulate TGF-β signalling, unveiling the regulatory controls governing this crucial pathway. Furthermore, we provide compelling evidence of the impact of circRNA-mediated TGF-β modulation on key cellular processes, including epithelial-mesenchymal transition (EMT), migration, and cell proliferation. In addition to their mechanistic roles, circRNAs have shown promise as diagnostic and prognostic biomarkers, as well as potential molecular targets for cancer therapy. Their ability to modulate critical pathways, such as the TGF-β signalling axis, underscores their significance in cancer biology and clinical applications. The intricate interplay between circRNAs and TGF-β is dissected, uncovering novel regulatory circuits that contribute to the complexity of cancer biology. This review unravels a previously unexplored dimension of carcinogenesis, emphasizing the crucial role of circRNAs in shaping the TGF-β signalling landscape.

Circular RNA (circRNA) is a unique type of noncoding RNA molecule characterized by its closed-loop structure. Functionally versatile, circRNAs play pivotal roles in gene expression regulation, protein activity modulation, and participation in cell signaling processes. In the context of cancers of the digestive system, the Wnt signaling pathway holds particular significance. Anomalous activation of the Wnt pathway serves as a primary catalyst for the development of colorectal cancer. Extensive research underscores the notable participation of circRNAs associated with the Wnt pathway in the progression of digestive system tumors. These circRNAs exhibit pronounced dysregulation across esophageal cancer, gastric cancer, liver cancer, colorectal cancer, pancreatic cancer, and cholangiocarcinoma. Furthermore, the altered expression of circRNAs linked to the Wnt pathway correlates with prognostic factors in digestive system tumors. Additionally, circRNAs related to the Wnt pathway showcase potential as diagnostic, therapeutic, and prognostic markers within the realm of digestive system tumors. This comprehensive review outlines the interplay between circRNAs and the Wnt signaling pathway in cancers of the digestive system. It seeks to provide a comprehensive perspective on their association while delving into ongoing research that explores the clinical applications of circRNAs associated with the Wnt pathway.

Cancer cells exhibit altered metabolic pathways, prominently featuring enhanced glycolytic activity to sustain their rapid growth and proliferation. Dysregulation of glycolysis is a well-established hallmark of cancer and contributes to tumor progression and resistance to therapy. Increased glycolysis supplies the energy necessary for increased proliferation and creates an acidic milieu, which in turn encourages tumor cells' infiltration, metastasis, and chemoresistance. Circular RNAs (circRNAs) have emerged as pivotal players in diverse biological processes, including cancer development and metabolic reprogramming. The interplay between circRNAs and glycolysis is explored, illuminating how circRNAs regulate key glycolysis-associated genes and enzymes, thereby influencing tumor metabolic profiles. In this overview, we highlight the mechanisms by which circRNAs regulate glycolytic enzymes and modulate glycolysis. In addition, we discuss the clinical implications of dysregulated circRNAs in cancer glycolysis, including their potential use as diagnostic and prognostic biomarkers. All in all, in this overview, we provide the most recent findings on how circRNAs operate at the molecular level to control glycolysis in various types of cancer, including hepatocellular carcinoma (HCC), prostate cancer (PCa), colorectal cancer (CRC), cervical cancer (CC), glioma, non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer (GC). In conclusion, this review provides a comprehensive overview of the significance of circRNAs in cancer glycolysis, shedding light on their intricate roles in tumor development and presenting innovative therapeutic avenues.

Cancer is a broad name for a group of diseases in which abnormal cells grow out of control and are characterized by their complexity and recurrence. Although there has been progress in cancer therapy with the entry of precision medicine and immunotherapy, cancer incidence rates have increased globally. Non-coding RNAs in the form of circular RNAs (circRNAs) play crucial roles in the pathogenesis, clinical diagnosis, and therapy of different diseases, including cancer. According to recent studies, circRNAs appear to serve as accurate indicators and therapeutic targets for cancer treatment. However, circRNAs are promising candidates for cutting-edge cancer therapy because of their distinctive circular structure, stability, and wide range of capabilities; many challenges persist that decrease the applications of circRNA-based cancer therapeutics. Here, we explore the roles of circRNAs as a replacement for cancer therapy, highlight the main challenges facing circRNA-based cancer therapies, and discuss the key strategies to overcome these challenges to improve advanced innovative therapies based on circRNAs with long-term health effects.

Hirschsprung's disease (HSCR) is a congenital disorder characterized by the absence of ganglion cells in the colon, leading to various intestinal complications. The etiology of HSCR stems from complex genetic and environmental interactions, of which the intricate roles of non-coding RNAs (ncRNAs) are a key area of research. However, the roles of ncRNAs in the pathogenesis of HSCR have not been fully elucidated. In order to understand the variety of symptoms caused by HSCR and develop new therapeutic approaches, it is essential to understand the underlying biological genetic basis of HSCR. This review presents a comprehensive overview of the current understanding regarding the involvement of ncRNAs in HSCR, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Additionally, it provides a summary of the molecular mechanisms through which ncRNAs regulate the expression of genes related to the proliferation, migration, and differentiation of intestinal neural crest cells, thereby contributing to the advancement of HSCR research.

Circular RNAs (circRNAs) are a member of non-coding RNAs with no ability in encoding proteins and their aberrant dysregulation is observed in cancers. Their closed-loop structure has increased their stability, and they are reliable biomarkers for cancer diagnosis. Urological cancers have been responsible for high mortality and morbidity worldwide, and developing new strategies in their treatment, especially based on gene therapy, is of importance since these malignant diseases do not respond to conventional therapies. In the current review, three important aims are followed. At the first step, the role of circRNAs in increasing or decreasing the progression of urological cancers is discussed, and the double-edged sword function of them is also highlighted. At the second step, the interaction of circRNAs with molecular targets responsible for urological cancer progression is discussed, and their impact on molecular processes such as apoptosis, autophagy, EMT, and MMPs is highlighted. Finally, the use of circRNAs as biomarkers in the diagnosis and prognosis of urological cancer patients is discussed to translate current findings in the clinic for better treatment of patients. Furthermore, since circRNAs can be transferred to tumor via exosomes and the interactions in tumor microenvironment provided by exosomes such as between macrophages and cancer cells is of importance in cancer progression, a separate section has been devoted to the role of exosomal circRNAs in urological tumors. [ABSTRACT FROM AUTHOR]

This manuscript summarizes information on the diverse range of RNA molecules and their role as competing endogenous RNAs (ceRNAs). Moreover, it provides an overview of ceRNA regulatory networks and their applications in ruminant biology. Knowledge of co-expression networks has increased with microarrays, RNA-seq, and scRNA-seq characterizing molecular mediators across various biological scales, using sequences from numerous blood and tissue samples. By synthesizing existing knowledge, this study summarizes interactions between coding and non-coding RNAs through microRNA response elements (MREs), elucidating large-scale regulatory networks throughout the transcriptome that influence the expression and activities of various ceRNAs. Identification of non-coding RNAs with important regulatory functions will revolutionize understanding of RNA biology, shifting from an mRNA-centric model to a complex network of RNA crosstalk. The ceRNA networks offer a more comprehensive and arguably more realistic perspective compared to protein–protein interaction (PPI) networks and weighted gene co-expression networks (WGCN). These ceRNA regulatory networks can describe potential molecular regulatory mechanisms related to functional and economically important traits in ruminants, plus contribute to disease and pathology research, by elucidating pathogenesis and potential drug effects in disease and cancer models. Furthermore, they can provide insights into farm animal biology, e.g., reproductive traits in goats and sheep, regulation of fat metabolism in beef cattle, heat stress responses, and lactation regulation in dairy cattle, fertility and muscle characteristics in buffalo, and resistance to high-salt and water-deprivation conditions in camels. In conclusion, ceRNA and associated regulatory networks should promote a new understanding of molecular mechanisms and identify candidate genes and metabolic-signaling pathways in ruminants.

Cancer poses intricate challenges to treatment due to its complexity and diversity. Ferroptosis and circular RNAs (circRNAs) are emerging as innovative therapeutic avenues amid the evolving landscape of cancer therapy. Extensive investigations into circRNAs reveal their diverse roles, ranging from molecular regulators to pivotal influencers of ferroptosis in cancer cell lines. The results underscore the significance of circRNAs in modulating molecular pathways that impact crucial aspects of cancer development, including cell survival, proliferation, and metastasis. A detailed analysis delineates these pathways, shedding light on the molecular mechanisms through which circRNAs influence ferroptosis. Building upon recent experimental findings, the study evaluates the therapeutic potential of targeting circRNAs to induce ferroptosis. By identifying specific circRNAs associated with the etiology of cancer, this analysis paves the way for the development of targeted therapeutics that exploit vulnerabilities in cancer cells. This review consolidates the existing understanding of ferroptosis and circRNAs, emphasizing their role in cancer therapy and providing impetus for ongoing research in this dynamic field.

Abstract Background Osteoporosis is a crucial health concern interconnected with physical disabilities as well as financial burdens. It arises from an imbalance between osteoblasts and osteoclasts, provoking the reduction of bone mass and the disturbances in bone structure with high fracture risk. Considerable efforts were done to prevent and mitigate this public health issue. Nonetheless, further understanding of the etiopathology of osteoporosis and the underlying genetic and epigenetic pathways is required. Main body Emerging evidence indicates that noncoding RNAs, including long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play crucial roles as epigenetic regulators in various pathological processes, including osteoporosis. LncRNAs are RNA transcripts with higher structural complexity that are developed owing to their secondary and tertiary structures, which allow them to create different binding sites for other biomolecules, such as DNA, RNA, and proteins. Another class of noncoding RNAs is circRNAs, which have a covalently closed loop structure without the 5′ cap and 3′ polyA tail and are formed by back-splicing of pre-mRNAs. Because of their closed structure, circRNAs are largely stable, resistant to RNA-degrading nucleases, and possess substantially longer circulatory half-lives than linear RNAs. Interestingly, both lncRNAs and circRNAs serve as competing endogenous RNAs by sponging multiple miRNA binding sites as well as interact with RNA-binding proteins (RBPs), thereby controlling the expression of their target genes. Several studies indicated that altered expression of these regulators could influence many biological processes in bone cells. Conclusion The current review provides current opinions on the role and the underlying mechanisms by which lncRNAs and circRNAs affect osteoblastic and osteoclastic activities. The deep understanding of these noncoding RNAs in osteoporosis offers distinctive avenues for innovative treatment strategies.

Abstract Background Refractoriness to surgical resection and chemotherapy makes intrahepatic cholangiocarcinoma (ICC) a fatal cancer of the digestive system with high mortality and poor prognosis. Important function invests circRNAs with tremendous potential in biomarkers and therapeutic targets. Nevertheless, it is still unknown how circRNAs contribute to the evolution of ICC. Methods CircRNAs in paired ICC and adjacent tissues were screened by circRNAs sequencing. To explore the impact of circRNAs on ICC development, experiments involving gain and loss of function were conducted. Various experimental techniques, including quantitative real-time PCR (qPCR), western blotting, RNA immunoprecipitation (RIP), luciferase reporter assays, RNA pull-down, chromatin immunoprecipitation (ChIP), ubiquitination assays and so on were employed to identify the molecular regulatory role of circRNAs. Results Herein, we reported a new circRNA, which originates from exon 9 to exon 15 of the SLCO1B3 gene (named circSLCO1B3), orchestrated ICC progression by promoting tumor proliferation, metastasis and immune evasion. We found that the circSLCO1B3 gene was highly overexpressed in ICC tissues and related to lymphatic metastasis, tumor sizes, and tumor differentiation. Mechanically, circSLCO1B3 not only promoted ICC proliferation and metastasis via miR-502-5p/HOXC8/SMAD3 axis, but also eradicated anti-tumor immunity via suppressing ubiquitin-proteasome-dependent degradation of PD-L1 by E3 ubiquitin ligase SPOP. We further found that methyltransferase like 3 (METTL3) mediated the m6A methylation of circSLCO1B3 and stabilizes its expression. Our findings indicate that circSLCO1B3 is a potential prognostic marker and therapeutic target in ICC patients. Conclusions Taken together, m6A-modified circSLCO1B3 was correlated with poor prognosis in ICC and promoted ICC progression not only by enhancing proliferation and metastasis via potentiating HOXC8 expression, but also by inducing immune evasion via antagonizing PD-L1 degradation. These results suggest that circSLCO1B3 is a potential prognostic marker and therapeutic target for ICC.

Abstract Background Cow milk fat is an essential indicator for evaluating and measuring milk quality and cow performance. Growing research has identified the molecular functions of circular RNAs (circRNAs) necessary for mammary gland development and lactation in mammals. Method The present study analyzed circRNA expression profiling data in mammary epithelial cells (MECs) from cows with highly variable milk fat percentage (MFP) using differential expression analysis and weighted gene co-expression network analysis (WGCNA). Results A total of 309 differentially expressed circRNAs (DE-circRNAs) were identified in the high and low MFP groups. WGCNA analysis revealed that the pink module was significantly associated with MFP (r = − 0.85, P = 0.007). Parental genes of circRNAs in this module were enriched mainly in lipid metabolism-related signaling pathways, such as focal adhesion, ECM-receptor interaction, adherens junction and AMPK. Finally, six DE-circRNAs were screened from the pink module: circ_0010571, circ_0007797, circ_0002746, circ_0003052, circ_0004319, and circ_0012840. Among them, circ_0002746, circ_0003052, circ_0004319, and circ_0012840 had circular structures and were highly expressed in mammary tissues. Subcellular localization revealed that these four DE-circRNAs may play a regulatory role in the mammary glands of dairy cows, mainly as competitive endogenous RNAs (ceRNAs). Seven hub target genes (GNB1, GNG2, PLCB1, PLCG1, ATP6V0C, NDUFS4, and PIGH) were obtained by constructing the regulatory network of their ceRNAs and then analyzed by CytoHubba and MCODE plugins in Cytoscape. Functional enrichment analysis revealed that these genes are crucial and most probable ceRNA regulators in milk fat metabolism. Conclusions Our study identified several vital circRNAs and ceRNAs affecting milk fat synthesis, providing new research ideas and a theoretical basis for cow lactation, milk quality, and breed improvement.

Botrytis cinerea is one of the main pathogens that harm the tomato yield and cause huge economic losses worldwide. Studies of circRNAs in response to the stress caused by pathogens have received more and more attention in tomato and other model crops. In this study, four groups were treated with ZaoFen (ZF), CuiLi (CL) (susceptible and tolerant genotypes to B. cinerea, respectively), ZFBc, CLBc (48 hour response to a B. cinerea infection). A total of 918 circRNAs were identified, among which exonic circRNAs (70.70%) accounted for the majority of them, and 118 circRNAs (12.85%) were located in chr1. A total of 18 (1.96%) circRNAs were shared among the four libraries. A total of 6 circRNAs showed fold changes in the differential expression analysis between the time and cultivar control groups, and circRNA115, circRNA145 and circRNA223 repeatedly appeared in the different control treatments. Notably, the gene targeted by circRNA115 was an ethylene-forming enzyme. At the same time, we predicted the target genes of the six circRNAs obtained in the study, and a total of 319 miRNAs were predicted. This study contributes to the mechanism in response to B. cinerea stress in the tomato, and paves the way for the further study of circRNAs under tomato pathogen stress.

Abstract Circular RNAs (CircRNAs) are now under discussion as novel promising biomarkers for patients with various tumors. Our study aimed to identify circRNAs related to the progression of colon cancer and to further investigate their roles in the development of colon cancer base on The Cancer Genome Atlas database. The competing endogenous RNA (ceRNA) network was constructed based on 4 circRNAs, 14 miRNAs, and 229 mRNAs. Meanwhile, three hub genes were identified via the protein protein interaction networks (PPI) network. It should be noted that only RUNX1 targeted by circ‐0084615 and mir‐330‐3p was confirmed as a survival‐related gene. Further analyses indicated the possible function of RUNX1 in colon progression, such as angiogenesis, epithelial–mesenchymal transition, hedgehog signaling and so on. Further investigations were conducted into the correlation between RUNX1 expression profiles and immune cells. Finally, we validated the expression of the circ‐0084615/mir‐330‐3p/RUNX1 axis in clinical specimens. In conclusion, we constructed ceRNA network and revealed that the circ‐0084615/mir‐330‐3p/RUNX1 axis serves as a critical role in colon cancer.

Abstract Background Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure. Methods The whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids (n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335). Results Anlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels. Conclusions CircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.

Abstract Background Acute myocardial infarction (AMI) is a serious cardiovascular disease that adversely affects human health. Circular RNAs (circRNAs) are involved in the pathological and physiological processes of AMI, but the biological mechanism of their involvement and their clinical significance remain unknown. We aimed to identify circRNAs that are significantly associated with morbidity in the peripheral blood of patients with AMI and evaluate their diagnostic utility. Methods High-throughput sequencing was used to screen for differentially expressed circRNAs in peripheral blood samples obtained from five patients with AMI and five sex- and age-matched healthy controls. A series of bioinformatics tools and databases were used to determine the biological functional classification and pathway enrichment of the circRNAs based on data obtained from sequencing. A hypoxia model was established and used to evaluate the effect of hypoxia on circRNA expression in human cardiomyocytes. A cytoplasmic separation assay and enzyme resistance assay were employed to identify the biological characteristics of circRNA. Polymerase chain reaction validity testing and receiver operating characteristic (ROC) curve analysis were used to evaluate the utility of circRNA assessments in the diagnosis of AMI. Results A large number of circRNAs were found to be differentially expressed in the peripheral blood of patients with AMI, and significantly more of these circRNAs were highly expressed than lowly expressed. The genes encoding these circRNAs have a wide range of effects on various functions in the body. A hypoxic environment promoted the upregulation of circRNA expression in human cardiomyocytes, and hsa_circ_0116795 encoded by PPARA was highly expressed in the peripheral blood of the patients with AMI. In terms of biological characteristics, under physiological conditions, hsa_circ_0116795 (circ_PPARA) was mainly located in the cytoplasm of cardiomyocytes and found to be resistant to exonuclease. The ROC curve analysis showed that the expression levels of circ_PPARA in the peripheral blood of patients with AMI were significantly different from those in the peripheral blood of healthy controls. Conclusion A large number of abnormally expressed circRNAs are detectable in the peripheral blood of patients with AMI. In particular, circ_PPARA is highly expressed in human myocardial cells under hypoxic conditions, and its biological characteristics indicate that it could be employed as a biomarker for the early diagnosis of AMI.

Circular RNAs (circRNAs) and small non-coding RNAs of the head-to-junction circle in the construct play critical roles in gene regulation and are significantly associated with breast cancer (BC). Numerous circRNAs are potential cancer biomarkers that may be used for diagnosis and prognosis. Widespread expression of circRNAs is regarded as a feature of gene expression in highly diverged eukaryotes. Recent studies show that circRNAs have two main biological modulation models: sponging and RNA-binding. This review explained the biogenesis of circRNAs and assessed emerging findings on their sponge function and role as RNA-binding proteins (RBPs) to better understand how their interaction alters cellular function in BC. We focused on how sponges significantly affect the phenotype and progression of BC. We described how circRNAs exercise the translation functions in ribosomes. Furthermore, we reviewed recent studies on RBPs, and post-protein modifications influencing BC and provided a perspective on future research directions for treating BC.

Intracranial aneurysms (IAs) present a substantial health threat, given the potential for catastrophic ruptures and subarachnoid hemorrhages (SAH). Swift and effective measures for diagnosis and treatment are paramount to enhance patient outcomes and alleviate the associated healthcare burden. In this context, circular RNAs (circRNAs) have emerged as an intriguing area of investigation, offering promise as both diagnostic biomarkers and therapeutic targets for IAs. CircRNAs have demonstrated their influence on critical molecular and cellular processes underpinning IAs pathogenesis, revealing their pivotal role in understanding this complex ailment. Beyond their diagnostic potential, circRNAs hold great potential as prognostic markers, providing crucial insights into IAs rupture risk. The unique circular structure and their regulatory functions make circRNAs an enticing avenue for innovative therapeutic approaches. The ongoing study of circRNAs in the context of IAs is an exciting and rapidly evolving field that has the potential to revolutionize approaches to diagnosis, treatment, and prevention of this life-threatening condition. As research continues to unravel the intricate roles of circRNAs, they are poised to become invaluable tools in clinical practice, enhancing patient care and ultimately reducing the impact of cerebral aneurysms on both individuals and healthcare systems. This comprehensive review delves deeply into the world of circRNAs in the realm of IAs, elucidating their multifaceted roles in the onset and progression of this condition. Moreover, this review ventures into the diagnosis and therapeutic potential of circRNAs, exploring their possible applications in gene therapy and as targets for novel treatment modalities.

CC (CC) remains a significant global health concern, imposing a substantial health burden on women worldwide due to its high incidence and mortality rates. To address this issue, there is a need for ongoing research to uncover the underlying molecular mechanisms of CC and to discover novel diagnostic and therapeutic strategies. Recent progress in non-coding RNAs (ncRNAs) has opened new avenues for investigation, and circular RNAs (circRNAs) have emerged as molecules with diverse roles in various cellular processes. These circRNAs are distinct in structure, forming a closed loop, setting them apart from their linear counterparts. They are intricately involved in regulating different aspects of cellular functions, particularly in cell growth and development. Remarkably, circRNAs can have varying functions, either promoting or inhibiting oncogenic processes, depending on the specific cellular context. Recent studies have identified abnormal circRNAs expression patterns associated with CC, indicating their significant involvement in disease development. The differing circRNAs profiles linked to CC present promising opportunities for early detection, precise prognosis evaluation, and personalized treatment strategies. In this comprehensive review, we embark on a detailed exploration of CC-related circRNAs, elucidating their distinct roles and providing insights into the intricate molecular mechanisms governing CC's onset and progression. A growing body of evidence strongly suggests that circRNAs can serve as valuable biomarkers for early CC detection and hold potential as therapeutic targets for intervention. By delving into the complex interplay between circRNAs and CC, we are paving the way for innovative, individualized approaches to combat this serious disease, with the goal of reducing its impact on women's health globally and improving patient outcomes. As our understanding of circRNAs in the context of CC continues to deepen, the outlook for breakthroughs in diagnosis and treatment becomes increasingly promising.

Background Brain tissue-derived extracellular vesicles (bdEVs) act locally in the central nervous system (CNS) and may indicate molecular mechanisms in human immunodeficiency virus (HIV) CNS pathology. Using brain homogenate (BH) and bdEVs from a simian immunodeficiency virus (SIV) model of HIV disease, we identified RNA networks in SIV infection and neuroinflammation. Methods Postmortem occipital cortex samples were obtained from uninfected controls and SIV-infected subjects (acute and chronic phases with or without CNS pathology [SIV encephalitis]). bdEVs were separated and characterized per international consensus guidelines. RNAs from bdEVs and BH were sequenced and quantitative polymerase chain reaction (qPCR)-amplified to detect levels of small RNAs (sRNAs, including microRNAs [miRNAs]) and longer RNAs including messenger RNAs (mRNAs) and circular RNAs (circRNAs). Results Dysregulated RNAs in BH and bdEVs were identified in acute and chronic infection with pathology groups, including mRNAs, miRNAs, and circRNAs. Most dysregulated mRNAs in bdEVs reflected dysregulation in source BH. These mRNAs are disproportionately involved in inflammation and immune responses. Based on target prediction, several circRNAs that were differentially abundant in source tissue might be responsible for specific differences in sRNA levels in bdEVs during SIV infection. Conclusions RNA profiling of bdEVs and source tissues reveals potential regulatory networks in SIV infection and SIV-related CNS pathology. [ABSTRACT FROM AUTHOR]

The non-coding RNAs comprise a large part of human genome lack of capacity in encoding functional proteins. Among various members of non-coding RNAs, the circular RNAs (circRNAs) have been of importance in the pathogenesis of human diseases, especially cancer. The circRNAs have a unique closed loop structure and due to their stability, they are potential diagnostic and prognostic factors in cancer. The increasing evidences have highlighted the role of circRNAs in the modulation of proliferation and metastasis of cancer cells. On the other hand, metastasis has been responsible for up to 90% of cancer-related deaths in patients, requiring more investigation regarding the underlying mechanisms modulating this mechanism. EMT enhances metastasis and invasion of tumor cells, and can trigger resistance to therapy. The cells demonstrate dynamic changes during EMT including transformation from epithelial phenotype into mesenchymal phenotype and increase in N-cadherin and vimentin levels. The process of EMT is reversible and its reprogramming can disrupt the progression of tumor cells. The aim of current review is to understanding the interaction of circRNAs and EMT in human cancers and such interaction is beyond the regulation of cancer metastasis and can affect the response of tumor cells to chemotherapy and radiotherapy. The onco-suppressor circRNAs inhibit EMT, while the tumor-promoting circRNAs mediate EMT for acceleration of carcinogenesis. Moreover, the EMT-inducing transcription factors can be controlled by circRNAs in different human tumors. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most common form of dementia. There are two main types of AD: familial and sporadic. Familial AD is linked to mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2). On the other hand, sporadic AD is the more common form of the disease and has genetic, epigenetic, and environmental components that influence disease onset and progression. Investigating the epigenetic mechanisms associated with AD is essential for increasing understanding of pathology and identifying biomarkers for diagnosis and treatment. Chemical covalent modifications on DNA and RNA can epigenetically regulate gene expression at transcriptional and posttranscriptional levels and play protective or pathological roles in AD and other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Refractoriness to surgical resection and chemotherapy makes intrahepatic cholangiocarcinoma (ICC) a fatal cancer of the digestive system with high mortality and poor prognosis. Important function invests circRNAs with tremendous potential in biomarkers and therapeutic targets. Nevertheless, it is still unknown how circRNAs contribute to the evolution of ICC. Methods: CircRNAs in paired ICC and adjacent tissues were screened by circRNAs sequencing. To explore the impact of circRNAs on ICC development, experiments involving gain and loss of function were conducted. Various experimental techniques, including quantitative real-time PCR (qPCR), western blotting, RNA immunoprecipitation (RIP), luciferase reporter assays, RNA pull-down, chromatin immunoprecipitation (ChIP), ubiquitination assays and so on were employed to identify the molecular regulatory role of circRNAs. Results: Herein, we reported a new circRNA, which originates from exon 9 to exon 15 of the SLCO1B3 gene (named circSLCO1B3), orchestrated ICC progression by promoting tumor proliferation, metastasis and immune evasion. We found that the circSLCO1B3 gene was highly overexpressed in ICC tissues and related to lymphatic metastasis, tumor sizes, and tumor differentiation. Mechanically, circSLCO1B3 not only promoted ICC proliferation and metastasis via miR-502-5p/HOXC8/SMAD3 axis, but also eradicated anti-tumor immunity via suppressing ubiquitin-proteasome-dependent degradation of PD-L1 by E3 ubiquitin ligase SPOP. We further found that methyltransferase like 3 (METTL3) mediated the m6A methylation of circSLCO1B3 and stabilizes its expression. Our findings indicate that circSLCO1B3 is a potential prognostic marker and therapeutic target in ICC patients. Conclusions: Taken together, m6A-modified circSLCO1B3 was correlated with poor prognosis in ICC and promoted ICC progression not only by enhancing proliferation and metastasis via potentiating HOXC8 expression, but also by inducing immune evasion via antagonizing PD-L1 degradation. These results suggest that circSLCO1B3 is a potential prognostic marker and therapeutic target for ICC. [ABSTRACT FROM AUTHOR]

Background: Chordoma, a rare bone tumour with aggressive local invasion and high recurrence rate with limited understanding of its molecular mechanisms. Circular RNAs (circRNAs) have been extensively implicated in tumorigenesis, yet their involvement in chordoma remains largely unexplored. N6‐methyladenosine (m6A) modification holds a crucial function in regulating protein translation, RNA degradation and transcription. Methods: Initially, screening and validation of circTEAD1 in chordoma were conducted by high‐throughput sequencing. Subsequently, sh‐circTEAD1 and an overexpression plasmid were constructed. Colony formation assays, cell counting kit‐8, Transwell and wound healing assays were utilized to validate the function of circTEAD1 in vitro. RNA pull‐down assays identified the binding proteins of circTEAD1, which underwent verification through RNA immunoprecipitation (RIP). Methylated RIP assays were conducted to detect the m6A binding sites. Following this, luciferase assay, RT‐qPCR, RIP and Western blotting analyses were conducted, revealing that Yap1 was the direct target of circTEAD1. Afterwards, the same methods were utilized for the validation of the function of Yap1 in chordoma in vitro. Finally, the regulatory relationship between circTEAD1 and Yap1 in chordoma was verified by an in vivo tumour formation assay. Results: CircTEAD1 was identified as an upregulated circRNA in chordoma specimens, with heightened circTEAD1 expression emerging as a prognostic indicator. In vitro experiments convincingly demonstrated that circTEAD1 significantly promoted chordoma cell invasion, migration and aggressiveness. Furthermore, the analysis revealed that methyltransferase‐like 3‐mediated m6A modification facilitated the cytoplasmic export of circTEAD1. The circTEAD1/IGF2BP3/Yap1 mRNA RNA‐protein ternary complex not only bolstered the stability of Yap1 mRNA but also exerted a pivotal role in driving chordoma tumorigenesis. Conclusions: In this study, the role of m6A‐modified circTEAD1 in chordoma was identified. The findings offer novel insights into the potential molecular targets for chordoma therapy, shedding light on the intricate interplay between circRNAs, m6A modification and Yap1 mRNA in chordoma pathogenesis. [ABSTRACT FROM AUTHOR]

In the event of a large-scale radiological accident, rapid and high-throughput biodosimetry is the most vital basis in medical resource allocation for the prompt treatment of victims. However, the current biodosimeter is yet to be rapid and high-throughput. Studies have shown that ionizing radiation modulates expressions of circular RNAs (circRNAs) in healthy human cell lines and tumor tissue. circRNA expressions can be quantified rapidly and high-throughput. However, whether circRNAs are suitable for early radiation dose classification remains unclear. We employed transcriptome sequencing and bioinformatics analysis to screen for radiation-differentially expressed circRNAs in the human lymphoblastoid cell line AHH-1 at 4 h following exposure to 0, 2, and 5 Gy 60Co γ-rays. The dose–response relationships between differentially expressed circRNA expressions and absorbed doses were investigated using real-time polymerase chain reaction and linear regression analysis at 4 h, 24 h, and 48 h post-exposure to 0, 2, 4, 6, and 8 Gy. Six distinct dose classification models of circRNA panels were established and validated by receiver operating characteristic (ROC) curve analysis. A total of 11 radiation-differentially expressed circRNAs were identified and validated. Based on dose–response effects, those circRNAs changed in a dose-responsive or dose-dependent manner were combined into panels A through F at 4 h, 24 h, and 48 h post-irradiation. ROC curve analysis showed that panels A through C had the potential to effectively classify exposed and non-exposed conditions, which area under the curve (AUC) of these three panels were all 1.000, and the associate p values were.009. Panels D through F excellently distinguished between different dose groups (AUC = 0.963–1.000, p <.05). The validation assay showed that panels A through F demonstrated consistent excellence in sensitivity and specificity in dose classification. Ionizing radiation can indeed modulate the circRNA expression profile in the human lymphoblastoid cell line AHH-1. The differentially expressed circRNAs exhibit the potential for rapid and high-throughput dose classification. [ABSTRACT FROM AUTHOR]

Historically, the Y chromosome has presented challenges to classical methodology and philosophy of understanding the differences between males and females. A genetic unsolved puzzle, the Y chromosome was the last chromosome to be fully sequenced. With the advent of the Human Genome Project came a realization that the human genome is more than just genes encoding proteins, and an entire universe of RNA was discovered. This dark matter of biology and the black box surrounding the Y chromosome have collided over the last few years, as increasing numbers of non-coding RNAs have been identified across the length of the Y chromosome, many of which have played significant roles in disease. In this review, we will uncover what is known about the connections between the Y chromosome and the non-coding RNA universe that originates from it, particularly as it relates to long non-coding RNAs, microRNAs and circular RNAs. [ABSTRACT FROM AUTHOR]

Aging is a multifactorial process characterized by an age-related decline in organismal fitness. This deterioration is the major risk factor for chronic diseases such as cardiovascular pathologies, neurodegeneration, or cancer, and it represents one of the main challenges of modern society. Therefore, understanding why and how we age would be a fundamental pillar to design strategies to promote a healthy aging. In the last decades, the study of the molecular bases of disease has been revolutionized by the discovery of different types of noncoding RNAs (ncRNAs) with regulatory potential. In this work, we will review the implication of ncRNAs in aging, with the aim to provide a first approach to the different aging-associated ncRNAs, their mechanism of action, and their potential relevance as therapeutic targets and disease biomarkers. [ABSTRACT FROM AUTHOR]

Background: Cow milk fat is an essential indicator for evaluating and measuring milk quality and cow performance. Growing research has identified the molecular functions of circular RNAs (circRNAs) necessary for mammary gland development and lactation in mammals. Method: The present study analyzed circRNA expression profiling data in mammary epithelial cells (MECs) from cows with highly variable milk fat percentage (MFP) using differential expression analysis and weighted gene co-expression network analysis (WGCNA). Results: A total of 309 differentially expressed circRNAs (DE-circRNAs) were identified in the high and low MFP groups. WGCNA analysis revealed that the pink module was significantly associated with MFP (r = − 0.85, P = 0.007). Parental genes of circRNAs in this module were enriched mainly in lipid metabolism-related signaling pathways, such as focal adhesion, ECM-receptor interaction, adherens junction and AMPK. Finally, six DE-circRNAs were screened from the pink module: circ_0010571, circ_0007797, circ_0002746, circ_0003052, circ_0004319, and circ_0012840. Among them, circ_0002746, circ_0003052, circ_0004319, and circ_0012840 had circular structures and were highly expressed in mammary tissues. Subcellular localization revealed that these four DE-circRNAs may play a regulatory role in the mammary glands of dairy cows, mainly as competitive endogenous RNAs (ceRNAs). Seven hub target genes (GNB1, GNG2, PLCB1, PLCG1, ATP6V0C, NDUFS4, and PIGH) were obtained by constructing the regulatory network of their ceRNAs and then analyzed by CytoHubba and MCODE plugins in Cytoscape. Functional enrichment analysis revealed that these genes are crucial and most probable ceRNA regulators in milk fat metabolism. Conclusions: Our study identified several vital circRNAs and ceRNAs affecting milk fat synthesis, providing new research ideas and a theoretical basis for cow lactation, milk quality, and breed improvement. [ABSTRACT FROM AUTHOR]

White adipose tissue (WAT) serves as the primary site for energy storage and endocrine regulation in mammals, while brown adipose tissue (BAT) is specialized for thermogenesis and energy expenditure. The conversion of white adipocytes to brown-like fat cells, known as browning, has emerged as a promising therapeutic strategy for reversing obesity and its associated co-morbidities. Noncoding RNAs (ncRNAs) are a class of transcripts that do not encode proteins but exert regulatory functions on gene expression at various levels. Recent studies have shed light on the involvement of ncRNAs in adipose tissue development, differentiation, and function. In this review, we aim to summarize the current understanding of ncRNAs in adipose biology, with a focus on their role and intricate mechanisms in WAT browning. Also, we discuss the potential applications and challenges of ncRNA-based therapies for overweight and its metabolic disorders, so as to combat the obesity epidemic in the future. [ABSTRACT FROM AUTHOR]