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Circular RNAs (circRNAs) are a subclass of non-coding RNAs which have demonstrated potential as biomarkers for Alzheimer’s disease (AD). In this study, we conducted a comprehensive exploration of the circRNA transcriptome within AD brain tissues. Specifically, we assessed circRNA expression patterns in the dorsolateral prefrontal cortex collected from nine AD-afflicted individuals and eight healthy controls. Utilising two circRNA detection tools, CIRI2 and CIRCexplorer2, we detected thousands of circRNAs and performed a differential expression analysis. CircRNAs which exhibited statistically significantly differential expression were identified as AD-specific differentially expressed circRNAs. Notably, our investigation revealed 120 circRNAs with significant upregulation and 1325 circRNAs displaying significant downregulation in AD brains when compared to healthy brain tissue. Additionally, we explored the expression profiles of the linear RNA counterparts corresponding to differentially expressed circRNAs in AD-afflicted brains and discovered that the linear RNA counterparts exhibited no significant changes in the levels of expression. We used CRAFT tool to predict that circUBE4B had potential to target miRNA named as hsa-miR-325-5p, ultimately regulated CD44 gene. This study provides a comprehensive overview of differentially expressed circRNAs in the context of AD brains, underscoring their potential as molecular biomarkers for AD. These findings significantly enhance our comprehension of AD’s underlying pathophysiological mechanisms, offering promising avenues for future diagnostic and therapeutic developments. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are non-coding RNAs generated by reverse splicing. They are involved in biological process and human diseases by interacting with specific RNA-binding proteins (RBPs). Due to traditional biological experiments being costly, computational methods have been proposed to predict the circRNA-RBP interaction. However, these methods have problems of single feature extraction. Therefore, we propose a novel model called circ-FHN, which utilizes only circRNA sequences to predict circRNA-RBP interactions. The circ-FHN approach involves feature coding and a hybrid deep learning model. Feature coding takes into account the physicochemical properties of circRNA sequences and employs four coding methods to extract sequence features. The hybrid deep structure comprises a convolutional neural network (CNN) and a bidirectional gated recurrent unit (BiGRU). The CNN learns high-level abstract features, while the BiGRU captures long-term dependencies in the sequence. To assess the effectiveness of circ-FHN, we compared it to other computational methods on 16 datasets and conducted ablation experiments. Additionally, we conducted motif analysis. The results demonstrate that circ-FHN exhibits exceptional performance and surpasses other methods. circ-FHN is freely available at https://github.com/zhaoqi106/circ-FHN. [ABSTRACT FROM AUTHOR]

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]

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]

Cardiovascular diseases (CVDs) pose a significant burden on global health. Developing effective diagnostic, therapeutic, and prognostic indicators for CVDs is critical. This narrative review explores the role of select non-coding RNAs (ncRNAs) and provides an in-depth exploration of the roles of miRNAs, lncRNAs, and circRNAs in different aspects of CVDs, offering insights into their mechanisms and potential clinical implications. The review also sheds light on the diverse functions of ncRNAs, including their modulation of gene expression, epigenetic modifications, and signaling pathways. It comprehensively analyzes the interplay between ncRNAs and cardiovascular health, paving the way for potential novel interventions. Finally, the review provides insights into the methodologies used to investigate ncRNA-mediated gene regulation in CVDs, as well as the implications and challenges associated with translating ncRNA research into clinical applications. Considering the broader implications, this research opens avenues for interdisciplinary collaborations, enhancing our understanding of CVDs across scientific disciplines. [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]

Neuropathic pain (NPP) is a refractory pain syndrome, caused by damage or disease of the somatosensory nervous system and characterized by spontaneous pain, hyperalgesia, abnormal pain and sensory abnormality. Non-coding RNAs (ncRNAs), including microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA) and Piwi interacting RNA (piRNA), play a notable role in initiation and maintenance of NPP. In this review, we summarize the role of ncRNAs in NPP and their underlaying mechanism. Generally, ncRNAs are interacted with mRNA, protein or DNA to regulate the molecules and signals assciated with neuroinflammation, ion channels, neurotrophic factors and others, and then involved in the occurrence and development of NPP. Therefore, this review not only contributes to deepen our understanding of the pathophysiological mechanism of NPP, but also provides theoretical basis for the development of new therapy strategies for this disorder. [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]

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]

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]

Thyroid cancer (TC) is one of the most common endocrine malignancies, and its incidence has increased globally. Despite extensive research, the underlying molecular mechanisms of TC remain partially understood, warranting continued exploration of molecular markers for diagnostic and prognostic applications. Circular RNAs (circRNAs) have recently garnered significant attention owing to their distinct roles in cancers. This review article introduced the classification and biological functions of circRNAs and summarized their potential as diagnostic and prognostic markers in TC. Further, the interplay of circRNAs with PI3K/Akt/mTOR, Wnt/β-catenin, MAPK/ERK, Notch, JAK/STAT, and AMPK pathways is elaborated upon. The article culminates with an examination of circRNA's role in drug resistance of TC and highlights the challenges in circRNA research in TC. [ABSTRACT FROM AUTHOR]

Purpose: Helicobacter pylori (H. pylori) has unique biochemical traits and pathogenic mechanisms, which make it a substantial cause of gastrointestinal cancers. Circular RNAs (circRNAs) have concurrently been identified as an important participating factor in the pathophysiology of several different cancers. However, the underlying processes and putative interactions between H. pylori and circRNAs have received very little attention. To address this issue, we explored the interaction between H. pylori and circRNAs to investigate how they might jointly contribute to the occurrence and development of gastric cancer. Methods: Changes in circPGD expression in H. pylori were detected using qRT-PCR. Cell proliferation and migration changes were assayed by colony formation, the CCK-8 assay and the transwell assay. Apoptosis was measured by flow cytometry. Western blot was conducted to detect changes in cell migration, apoptosis, proliferation and inflammation-associated proteins. QRT-PCR was used to measure changes in circPGD and inflammation-associated factors. Results: We found that H. pylori induced increased circPGD expression in infected human cells and facilitated gastric cancer progression in three ways by promoting cell proliferation and migration, enhancing the inflammatory response, and inhibiting apoptosis. Conclusions: CircPGD appears to play a role in H. pylori-related gastric cancer and may thus be a viable, novel target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that circular RNAs (circRNAs) accumulate in aging tissues and nonproliferating cells due to their high stability. However, whether upregulation of circRNA expression mediates stem cell senescence and whether circRNAs can be targeted to alleviate aging-related disorders remain unclear. Here, RNA sequencing analysis of differentially expressed circRNAs in long-term-cultured mesenchymal stem cells (MSCs) revealed that circSERPINE2 expression was significantly increased in late passages. CircSERPINE2 small interfering RNA delayed MSC senescence and rejuvenated MSCs, while circSERPINE2 overexpression had the opposite effect. RNA pulldown followed by mass spectrometry revealed an interaction between circSERPINE2 and YBX3. CircSERPINE2 increased the affinity of YBX3 for ZO-1 through the CCAUC motif, resulting in the sequestration of YBX3 in the cytoplasm, inhibiting the association of YBX3 with the PCNA promoter and eventually affecting p21 ubiquitin-mediated degradation. In addition, our results demonstrated that senescence-related downregulation of EIF4A3 gave rise to circSERPINE2. In vivo, intra-articular injection of si-circSerpine2 restrained native joint-resident MSC senescence and cartilage degeneration in mice with aging-related osteoarthritis. Taken together, our findings provide strong evidence for a regulatory role for the circSERPINE2/YBX3/PCNA/p21 axis in MSC senescence and the therapeutic potential of si-circSERPINE2 in alleviating aging-associated syndromes, such as osteoarthritis. [ABSTRACT FROM AUTHOR]

CircRNAs, a type of non-coding RNA widely present in eukaryotic cells, have emerged as a prominent focus in tumor research. However, the functions of most circRNAs remain largely unexplored. Known circRNAs exert their regulatory roles through various mechanisms, including acting as microRNA sponges, binding to RNA-binding proteins, and functioning as transcription factors to modulate protein translation and coding. Tumor growth is not solely driven by gene mutations but also influenced by diverse constituent cells and growth factors within the tumor microenvironment (TME). As crucial regulators within the TME, circRNAs are involved in governing tumor growth and metastasis. This review highlights the role of circRNAs in regulating angiogenesis, matrix remodeling, and immunosuppression within the TME. Additionally, we discuss current research on hypoxia-induced circRNAs production and commensal microorganisms' impact on the TME to elucidate how circRNAs influence tumor growth while emphasizing the significance of modulating the TME. [ABSTRACT FROM AUTHOR]

A circular RNA (circRNA) is a non-coding RNA (ncRNA) derived from reverse splicing from pre-mRNA and is characterized by the absence of a cap structure at the 5′ end and a poly-adenylated tail at the 3′ end. Owing to the development of RNA sequencing and bioinformatics approaches in recent years, the important clinical value of circRNAs has been increasingly revealed. Circ_0067934 is an RNA molecule of 170 nucleotides located on chromosome 3q26.2. Circ_0067934 is formed via the reverse splicing of exons 15 and 16 in PRKCI (protein kinase C Iota). Recent studies revealed the upregulation or downregulation of circ_0067934 in various tumors. The expression of circ_0067934 was found to be correlated with tumor size, TNM stage, and poor prognosis. Based on experiments with cancer cells, circ_0067934 promotes cancer cell proliferation, migratory activity, and invasion when overexpressed or downregulated. The potential mechanism involves the binding of circ_0067934 to microRNAs (miRNAs; miR-545, miR-1304, miR-1301-3p, miR-1182, miR-7, and miR-1324) to regulate the post-transcriptional expression of genes. Other mechanisms include inhibition of the Wnt/β-catenin and PI3K/AKT signaling pathways. Here, we summarized the biological functions and possible mechanisms of circ_0067934 in different tumors to enable further exploration of its translational applications in clinical diagnosis, therapy, and prognostic assessments. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) as small non-coding RNAs with cell, tissue, or organ-specific expression accomplish a broad array of functions in physiological and pathological processes such as cancer development. Angiogenesis, a complicated multistep process driving a formation of new blood vessels, speeds up tumor progression by supplying nutrients as well as energy. Abnormal expression of circRNAs reported to affect tumor development through impressing angiogenesis. Such impacts are introduced as constant with different tumorigenic features known as "hallmarks of cancer". In addition, deregulated circRNAs show possibilities to prognosis and diagnosis both in the prophecy of prognosis in malignancies and also their prejudice from healthy individuals. In the present review article, we have evaluated the angiogenic impacts and anti-angiogenic managements of circRNAs in human cancers. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are RNAs with closed circular structure involved in many biological processes by key interactions with RNA binding proteins (RBPs). Existing methods for predicting these interactions have limitations in feature learning. In view of this, we propose a method named circ2CBA, which uses only sequence information of circRNAs to predict circRNA-RBP binding sites. We have constructed a data set which includes eight sub-datasets. First, circ2CBA encodes circRNA sequences using the one-hot method. Next, a two-layer convolutional neural network (CNN) is used to initially extract the features. After CNN, circ2CBA uses a layer of bidirectional long and short-term memory network (BiLSTM) and the self-attention mechanism to learn the features. The AUC value of circ2CBA reaches 0.8987. Comparison of circ2CBA with other three methods on our data set and an ablation experiment confirm that circ2CBA is an effective method to predict the binding sites between circRNAs and RBPs. [ABSTRACT FROM AUTHOR]

Background: Advanced paternal age (APA) is associated with decreased fertility, but the mechanism underlying APA remains unknown. CircRNAs have been reported to be ideal candidate biomarkers for diagnostic and therapeutic applications in many diseases and are also involved in spermatogenesis. Hence, we aimed to assess the circRNA expression profile of spermatozoa from aging men. Methods and results: We recruited 6 subjects, including 3 in the younger group (men age < 40) and 3 in the APA group (men age ≥ 40). RNA sequencing was exploited to identify the expression profiles of circRNAs between the two groups. The expression levels of circRNAs were validated using real-time quantitative polymerase chain reaction (RT–qPCR). Kyoto Encyclopedia of Genes and Genomes biological pathway analysis and Gene Ontology analysis were performed to evaluate the functions of differentially expressed circRNAs (DE-circRNAs) between the two groups. In total, 18,787 circRNAs were sequenced in the spermatozoa of two groups. Our analysis revealed that there were 1056 downregulated circRNAs and 1228 upregulated circRNAs between the two groups, and KEGG analysis showed they were mainly involved in pathways including the DNA repair signaling pathway, meiotic recombination signaling pathway, and PI3K/AKT signaling pathway. Conclusions: In conclusion, our study suggested that circRNAs play a vital role in spermatozoa from aging men and provided a fresh perspective on the specific regulatory mechanism of spermatozoa from aging men. [ABSTRACT FROM AUTHOR]

Drought is a most common abiotic stress restricting crop yield and quality in the world. Although knowledge of circular RNAs (circRNAs) has been updated continuously and rapidly, information about circRNAs in the regulation of drought resistance is extremely limited in sugar beet. To unravel the mechanism of sugar beet circRNAs in drought stress response, genome-wide identification of sugar beet circRNAs was conducted under drought treatment via deep sequencing. A total of 17 differentially expressed circRNAs were identified under drought stress. As revealed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) outcomes, circRNAs could participate in the drought-responsive events. A circRNA–miRNA–mRNA network was constructed using the target genes directly or indirectly related to plant drought resistance based on some differentially expressed circRNAs. Novel_circ_0000442 and novel_circ_0000443 may act as sponges by targeting ath-miR157d to regulate the expression of its target genes including BVRB_1g004570, BVRB_1g005450 and BVRB_1g005790 involved in drought response. Some parent genes of drought-responsive cirRNAs were related to signal transduction and oxidation–reduction. Our results provide new insights into drought resistance mechanisms and lay a foundation for further studies exploring complex gene regulation networks in sugar beet. [ABSTRACT FROM AUTHOR]

Breast cancer is a complex and heterogeneous disease that poses a significant public health concern worldwide, and it remains a major challenge despite advances in treatment options. One of the main properties of cancer cells is the increased proliferative activity that has lost regulation. Dysregulation of various positive and negative modulators in the cell cycle has been identified as one of the driving factors of breast cancer. In recent years, non-coding RNAs have garnered much attention in the regulation of cell cycle progression, with microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs) being of particular interest. MiRNAs are a class of highly conserved and regulatory small non-coding RNAs that play a crucial role in the modulation of various cellular and biological processes, including cell cycle regulation. CircRNAs are a novel form of non-coding RNAs that are highly stable and capable of modulating gene expression at posttranscriptional and transcriptional levels. LncRNAs have also attracted considerable attention because of their prominent roles in tumor development, including cell cycle progression. Emerging evidence suggests that miRNAs, circRNAs and lncRNAs play important roles in the regulation of cell cycle progression in breast cancer. Herein, we summarized the latest related literatures in breast cancer that emphasize the regulatory roles of miRNAs, circRNAs and lncRNAs in cell cycle progress of breast cancer. Further understanding of the precise roles and mechanisms of non-coding RNAs in breast cancer cell cycle regulation could lead to the development of new diagnostic and therapeutic strategies for breast cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a malignant disease with a high incidence and low survival rate, and the effectiveness of traditional treatments, such as surgery and radiotherapy, is very limited. CircRNAs, a kind of stable endogenous circular RNA, generally function by sponging miRNAs and binding or translating proteins. CircRNAs have been identified to play an important role in regulating the proliferation and metabolism of CRC. In recent years, many reports have indicated that by regulating the expression of glycolysis-related proteins, such as GLUT1 and HK2, or directly translating proteins, circRNAs can promote the Warburg effect in cancer cells, thereby driving CRC metabolism. Moreover, the Warburg effect increases lactate production in cancer cells and promotes acidification of the TME, which further drives cancer progression. In this review, we summarized the remarkable role of circRNAs in regulating glucose metabolism in CRC in recent years, which might be useful for finding new targets for the clinical treatment of CRC. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is a cancer of the gastrointestinal tract that is highly malignant and has poor prognosis. Circular RNAs are a class of nonclassical RNA molecules that have been determined to be involved in GC malignancy in various ways. However, the underlying function and mechanism of circTDRD3 in gastric cancer remain largely unknown. Methods: We analyzed circTDRD3 expression in databases and verified the findings in GC cell lines and tissue specimens. A series of functional gene overexpression and knockdown assays in vivo and in vitro were carried out to investigate the role of circTDRD3 in proliferation and metastasis. Here, we revealed the role of the miR-891b/ITGA2 axis by analyzing bioinformatics datasets. Furthermore, we performed dual-luciferase, fluorescence in situ hybridization, RNA pull-down, and functional rescue experiments to examine the relationships between circTDRD3 and its interacting molecules. Western blot confirmed the positive regulatory role of circTDRD3 in the AKT signaling pathway. A promoting effect of ATF4 on circTDRD3 was determined through chromatin immunoprecipitation. Results: CircTDRD3 was significantly overexpressed in GC tissues compared with adjacent benign tissue, and its expression level was positively correlated with tumor volume and lymph node metastasis. CircTDRD3 promoted GC cell proliferation and migration in vitro and in vivo. Mechanistically, circTDRD3 exerted a tumor-promoting effect by regulating the miR-891b/ITGA2 axis and AKT signaling pathway in a positive feedback manner mediated by the transcription factor ATF4. Conclusions: ATF4-mediated circTDRD3 overexpression modulates the proliferation and metastasis of GC cells through the miR-891b/ITGA2 axis in a positive feedback manner. [ABSTRACT FROM AUTHOR]

Background: Over the last few decades, research associated with the coding genome, primarily DNA and transcriptome (mRNA, rRNA, and tRNA), has changed our understanding in several aspects, including physiology, diagnostics, and therapeutics. A large proportion of the human genome that encodes proteins is essential for physiology. However, the human genome represents a significantly large proportion of non-translational, i.e., non-coding (nc) RNAs like microRNAs, siRNAs, piRNAs, lncRNAs, and circRNAs. These ncRNAs do not translate into functional proteins but are associated with several events, such as the regulation of gene expression via several mechanisms. Our understanding of ncRNAs has advanced in the last decade, such as microRNAs and siRNAs, but still, several other ncRNAs remain unexplored. The study comprehended the association of ncRNAs in cerebral ischemia. Methods: In this study searches utilizing multiple databases, PubMed, EMBASE, and Google Scholar were made. The literature survey was done on ncRNA including short and lncRNA associated with the onset, and progression of cerebral ischemia. The literature search was also made for the studies associated with the diagnostic and therapeutic role of ncRNAs for cerebral ischemia. Results and discussion: Reports suggested that both short and long ncRNAs are critical players of gene expression and are hence associated with the pathophysiology of cerebral ischemia. The reports demonstrate ncRNAs precisely lncRNAs and microRNAs are not only associated with cerebral ischemia progression but also potential diagnostic and therapeutic candidates. In conclusion: This review is certainly helpful to understand the interplay of ncRNAs in understanding gene expression profile and pathophysiology of cerebral ischemia. These ncRNAs molecules show potential for diagnostic and therapeutic development. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are key regulators of cellular processes, are abundant in the nervous system, and have putative regulatory roles during neural differentiation. However, the knowledge about circRNA functions in brain development is limited. Here, using RNA-sequencing, we show that circRNA levels increased substantially over the course of differentiation of human embryonic stem cells into rostral and caudal neural progenitor cells (NPCs), including three of the most abundant circRNAs, ciRS-7, circRMST, and circFAT3. Knockdown of circFAT3 during early neural differentiation resulted in minor transcriptional alterations in bulk RNA analysis. However, single-cell transcriptomics of 30 and 90 days differentiated cerebral organoids deficient in circFAT3 showed a loss of telencephalic radial glial cells and mature cortical neurons, respectively. Furthermore, non-telencephalic NPCs in cerebral organoids showed changes in the expression of genes involved in neural differentiation and migration, including FAT4, ERBB4, UNC5C, and DCC. In vivo depletion of circFat3 in mouse prefrontal cortex using in utero electroporation led to alterations in the positioning of the electroporated cells within the neocortex. Overall, these findings suggest a conserved role for circFAT3 in neural development involving the formation of anterior cell types, neuronal differentiation, or migration. [ABSTRACT FROM AUTHOR]

Gallbladder cancer (GBC) performs strongly invasive and poor prognosis, and adenocarcinoma is the most common histological type in it. Statistically, the 5-year survival rate of patients with advanced GBC is less than 5%. Such dismal outcome might be caused by chemotherapy resistance and native biology of tumor cells, regardless of emerging therapeutic strategies. Early diagnosis, depending on biomarkers, receptors and secretive proteins, is more important than clinical therapy, guiding the pathologic stage of cancer and the choice of medication. Therefore, it is in urgent need to understand the specific pathogenesis of GBC and strive to find promising novel biomarkers for early screening in GBC. Non-coding RNAs (ncRNAs), especially microRNAs (miRNAs, miRs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are confirmed to participate in and regulate the occurrence and development of GBC. Exceptionally, lncRNAs and circRNAs could act as competing endogenous RNAs (ceRNAs) containing binding sites for miRNAs and crosstalk with miRNAs to target regulatory downstream protein-coding messenger RNAs (mRNAs), thus affecting the expression levels of specific proteins to participate in and regulate the development and progression of GBC. It follows that ncRNAs may become promising biomarkers and potential therapeutic targets for GBC. In this review, we mainly summarize the recent research progress of miRNAs and lncRNAs in regulating the development and progression of GBC, chemoresistance, and predicting the prognosis of patients, and highlight the potential applications of the lncRNA/circRNA–miRNA–mRNA cross-regulatory networks in early diagnosis, chemoresistance, and prognostic evaluation, aiming to better understand the pathogenesis of GBC and develop new diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

The development of skeletal muscle in animals is a complex biological process, which are strictly and precisely regulated by many genes and non-coding RNAs. Circular RNA (circRNA) was found as a novel class of functional non-coding RNA with ring structure in recent years, which appears in the process of transcription and is formed by covalent binding of single-stranded RNA molecules. With the development of sequencing and bioinformatics analysis technology, the functions and regulation mechanisms of circRNAs have attracted great attention due to its high stability characteristics. The role of circRNAs in skeletal muscle development have been gradually revealed, where circRNAs were involved in various biological processes, such as proliferation, differentiation, and apoptosis of skeletal muscle cells. In this review, we summarized the current studies advance of circRNAs involved in skeletal muscle development in bovine, and hope to gain a deeper understanding of the functional roles of the circRNAs in muscle growth. Our results will provide some theoretical supports and great helps for the genetic breeding of this species, and aiming at improving bovine growth and development and preventing muscle diseases. [ABSTRACT FROM AUTHOR]

Nowadays, drug resistance (DR) in gastrointestinal (GI) cancers, as the main reason for cancer-related mortality worldwide, has become a serious problem in the management of patients. Several mechanisms have been proposed for resistance to anticancer drugs, including altered transport and metabolism of drugs, mutation of drug targets, altered DNA repair system, inhibited apoptosis and autophagy, cancer stem cells, tumor heterogeneity, and epithelial-mesenchymal transition. Compelling evidence has revealed that genetic and epigenetic factors are strongly linked to DR. Non-coding RNA (ncRNA) interferences are the most crucial epigenetic alterations explored so far, and among these ncRNAs, circular RNAs (circRNAs) are the most emerging members known to have unique properties. Due to the absence of 5' and 3' ends in these novel RNAs, the two ends are covalently bonded together and are generated from pre-mRNA in a process known as back-splicing, which makes them more stable than other RNAs. As far as the unique structure and function of circRNAs is concerned, they are implicated in proliferation, migration, invasion, angiogenesis, metastasis, and DR. A clear understanding of the molecular mechanisms responsible for circRNAs-mediated DR in the GI cancers will open a new window to the management of GI cancers. Hence, in the present review, we will describe briefly the biogenesis, multiple features, and different biological functions of circRNAs. Then, we will summarize current mechanisms of DR, and finally, discuss molecular mechanisms through which circRNAs regulate DR development in esophageal cancer, pancreatic cancer, gastric cancer, colorectal cancer, and hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: Glioma is the most common malignant tumor in the central nervous system. In patients with glioma, the prognosis is poor and median survival is only 12–15 months. With the recent development of sequencing technology, important roles of noncoding RNAs are being discovered in cells, especially those of circular RNAs (circRNAs). Because circRNAs are stable, abundant, and highly conserved, they are regarded as novel biomarkers in the early diagnosis and prognosis of diseases. Purpose: In this review, roles and mechanisms of circRNAs in the development of glioma are summarized. Methods: This paper collects and reviews relevant PubMed literature. Conclusion: Several classes of circRNAs are highly expressed in glioma and are associated with malignant biological behaviors of gliomas, including proliferation, migration, invasion, apoptosis, angiogenesis, and drug resistance. Further studies are needed to clarify the roles of circRNAs in glioma and to determine whether it is possible to increase therapeutic effects on tumors through circRNA intervention. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs involved in several cellular and biological processes, including gene expression regulation, microRNA function, transcription regulation, and translation modification. Therefore, these non-coding RNAs have important roles in the pathogenesis of various diseases. Male infertility is mainly due to abnormal sperm parameters such as motility, morphology, and concentration. Recent studies have confirmed the role of circRNAs in spermatogenesis, and the expression of several circRNAs is confirmed in seminal plasma, spermatozoa, and testicular tissue. It is suggested that deregulation of circRNAs is involved in different types of male infertility, including azoospermia, oligozoospermia, and asthenozoospermia. In the present review, we aimed to discuss the potential roles of circRNAs in spermatogenesis failure, sperm defects, and male infertility. Due to their conserved and special structure and tissue-specific expression pattern, circRNAs can be applied as reliable noninvasive molecular biomarkers, therapeutic and pharmaceutical targets in male infertility. [ABSTRACT FROM AUTHOR]

With the rapid developments of bioinformatics technologies, various kinds of circRNAs in many species have been developed and the according pivotal roles were also revealed. However, a few studies describing circRNAs involved in seed development and oil biosynthesis processes have been reported, with no studies reported in sunflower (Helianthus annuus L.) to date. In this current research, using a kind of sunflower seed with its high oleic acid content, we first measured seed fresh weight, dry weight, and moisture content during different seed developmental stages. Next, high-throughput sequencing and bioinformatics methodologies were employed to detect circRNAs in seed specimens collected during three representative developmental stages. Ultimately, a total of 3482 new circRNAs were detected, of which 2723, 2910, and 1538 were found to be differentially expressed (DE) between paired time points of L7 vs. L22DAF, L7 vs. L37DAF, and L22 vs. L37DAF, respectively. Gene ontology (GO) analysis assigned lipid metabolism-associated GO functional terms to some host genes of DEcircRNAs. Notably, both KEGG functional pathway enrichment analysis results and GO results suggested that host DEcircRNA gene functions were correlated with pathways that in relation to fatty acid metabolism (FAM). Finally, networks comprised of DEcircRNAs and host genes with FAM pathway-associated functions were constructed. Results of network analysis highlighted important functional associations between DEcircRNAs and several key enzymes, including delta-12 desaturase (FAD2). These results revealed potential functional roles of circRNAs in sunflower, including regulatory roles in seed development and oil biosynthesis processes. This work also describes an effective strategy for investigating novel circRNAs in sunflower. [ABSTRACT FROM AUTHOR]

The modern categories of endogenous non-coding RNAs, namely circular RNAs (circRNAs), involved within the carcinogenesis and progression of various human cancers. The fundamental aim of the current investigation was the evaluation of the hsa_circ_0014130 expressions, their biological functions, and potential regulatory network in bladder cancer. The level of expression for hsa_circ_0014130 was evaluated by qRT-PCR, and its relationships to clinicopathological features and survival outcomes of cases experiencing cancer of the bladder were scrutinized. The impact of hsa_circ_0014130 expressions on biological attitudes of bladder cancer cells in vitro was investigated. The interactions between hsa_circ_0014130 and microRNA (miRNA) sponge, miRNA, and its direct targets were determined by RNA pull-down as well as luciferase reporter gene assay. The correlations of their expression were determined by Pearson's correlation analysis. Rescue experiments were carried out to identify the biological roles of the regulation network. The expressions of hsa_circ_0014130 were markedly ameliorated in bladder cancer samples and linked with aggressive characteristics and unfavorable survival. Ectopic expression of hsa_circ_0014130 clearly enhanced the differentiation, proliferative, migratory, invasive potential of the cell in bladder cancer, and the development of tumor xenograft in vivo, while malignant biological behaviors were inhibited by hsa_circ_0014130 knockdown. The expression of hsa_circ_0014130 was tied to miR-132-3p in a negative manner with the cells and tissues of bladder cancer. hsa_circ_0014130 function as a competitive endogenous RNA for miR-132-3p to play oncogenic roles in bladder cancer cells. On the other hand, KCNJ12 was a straightforward target of miR-132-3p at the downstream, and the expressions of KCNJ12 were inversely related to that of miR-132-3p. Furthermore, a significantly positive correlation was found between hsa_circ_0014130 and KCNJ12 mRNA expression. More importantly, the oncogenic impact of hsa_circ_0014130 on bladder cancer cells was partly suppressed by ectopic expression of miR-132-3p or KCNJ12 knockdown. The underlined data revealed that hsa_circ_0014130 exerted its biological roles by regulating miR-132-3p/KCNJ12 expression. Further research revealed hsa_circ_0014130/miR-132-3p/KCNJ12 axis has participated in the Epithelial-mesenchymal transition (EMT) progress and GSK3β/AKT signaling pathway. hsa_circ_0014130 works as a sponge of miR-132-3p to advance the oncogenesis and metastasis of bladder cancer by regulation of the KCNJ12 expression. These achievements might ameliorate the comprehension of tumor pathogenesis and provide novel therapeutic targets for cancer of the bladder. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that are more abundant, specific, and highly organized than linear RNAs. Increasing evidence supports that circRNAs may serve as diagnostic biomarkers in many diseases, but their potential as biomarkers in systemic lupus erythematosus (SLE) remains unclear. Objective: We investigated the critical circRNAs involved in SLE progression and explored their potential application as biomarkers in SLE. Method: RNA sequencing was conducted on peripheral blood mononuclear cells (PBMCs) from 4 SLE patients and 4 healthy volunteers. CircRNA profile data were analyzed to identify differentially expressed circRNAs and visualized via R software. After screening, qPCR analysis of target circRNA expression was performed using PBMCs from 31 SLE patients and 35 healthy volunteers. Correlations between circRNA expression levels and the SLEDAI score were assessed via Spearman correlation analysis. Finally, the performance of circRNAs as biomarkers in SLE was examined by receiver operating characteristic curve analysis. Results: The result identified six differentially expressed circRNAs between SLE patients and healthy controls: hsa_circ_0006689, hsa_circ_0070562, hsa_circ_0006117, hsa_circ_0007683, hsa_circ_0042519, and hsa_circ_0008647. The validation analysis showed differing relative expression levels of hsa_circ_0007683, hsa_circ_0042519, hsa_circ_0008647, and hsa_circ_0006689 between SLE patients and healthy volunteers (P < 0.05), and hsa_circ_0006689 expression in PBMCs correlated with the SLEDAI score (P < 0.05). Furthermore, addition of hsa_circ_0006689 expression increased the sensitivities of anti-dsDNA antibody and anti-Sm antibody levels for SLE diagnosis (from 29.03 to 61.30% and 32.26–71.00%, respectively). Conclusion: Our results suggest hsa_circ_0006689 may be a useful circRNA biomarker for SLE diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are an interesting class of conserved single-stranded RNA molecules derived from exon or intron sequences produced by the reverse splicing of precursor mRNA. CircRNAs play important roles as microRNA sponges, gene splicing and transcriptional regulators, RNA-binding protein sponges, and protein/peptide translation factors. Abnormal functions of circRNAs and RBPs in tumor progression have been widely reported. Insulin-like growth factor-2 mRNA-binding proteins (IGF2BPs) are a highly conserved family of RBPs identified in humans that function as post-transcriptional fine-tuners of target transcripts. Emerging evidence suggests that IGF2BPs regulate the processing and metabolism of RNA, including its stability, translation, and localization, and participate in a variety of cellular functions and pathophysiology. In this review, we have summarized the roles and molecular mechanisms of circRNAs and IGF2BPs in cancer development and progression. In addition, we briefly introduce the role of other RNAs and IGF2BPs in cancer, discuss the current clinical applications and challenges faced by circRNAs and IGF2BPs, and propose future directions for this promising research field. [ABSTRACT FROM AUTHOR]

To explore the expression profiles of mRNAs, long-noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and construct the competitive endogenous RNA networks in granulosa cells (GCs) of infertile women with ovarian endometriosis. RNA sequencing was conducted for RNA expression profiling from GCs of five women with ovarian endometriosis and five with tubal factor infertility. The differential expression of mRNAs, lncRNAs and circRNAs was compared. Then, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed. Finally, the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to determine the role of the differential expression of mRNA. A total of 12,498 mRNAs, 724 lncRNAs and 2269 circRNAs were identified in ovarian endometriosis and controls. 37 mRNAs, 51 lncRNAs and 101 circRNAs were detected to be differentially expressed in women with ovarian endometriosis. Ten lncRNAs and 22 differentially expressed mRNAs were selected to build the lncRNA–miRNA–mRNA network, while 12 circRNAs and four differentially expressed mRNAs were selected to build the circRNA–miRNA–mRNA network. GO analysis suggested that the differentially expressed mRNAs were mainly involved in regulation of cell differentiation, cell cycle while KEGG pathway analysis showed that pathways involved in the MAPK signaling pathway and FoxO signaling pathway were enriched with differentially upregulated mRNAs. We generated mRNAs, lncRNAs and circRNAs expression profiles and identified differentially expressed RNAs of GCs in infertile women with ovarian endometriosis. These findings provide a basis for further understanding of the underlying etiology of endometriosis-related infertility. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) play key roles in carcinogenesis. However, the roles of circRNAs in gastric cancer are largely unknown. The aim of this study is to study the possible roles of hsa_circ_0006282 in gastric cancer. Methods: The hsa_circ_0006282 levels in gastric cancer cell lines, 85 gastritis tissues, and 103 paired gastric cancer tissues and non-tumor tissues were first detected by quantitative real-time reverse transcription-polymerase chain reaction. RNA interference and hsa_circ_0006282 expression plasmid were further used to manipulate hsa_circ_0006282 expression in gastric cancer. Finally, biological effects of hsa_circ_0006282 were analyzed by real-time cell analysis, flow cytometry, Transwell, cell cloning assay and Western blot analysis. Results: Hsa_circ_0006282 was down expressed in gastric cancer cells, gastritis tissues, and gastric cancer tissues. The abilities of cell proliferation, cell migration and resistance to apoptosis were enhanced after hsa_circ_0006282 was downregulated, while overexpression of hsa_circ_0006282 got opposite results. Besides, Western blot showed that the levels of protein kinase B (AKT) and cyclin-dependent kinase 2 (CDK2) were significantly increased and decreased after knockdown and up-regulation of hsa_circ_0006282, respectively, while phosphatase and tensin homolog deleted on chromosome ten (PTEN) was significantly opposite regulated. Finally, hsa_circ_0006282 promoted the expression of PTEN by sponging hsa-miR-136-5p. Conclusion: By regulating the PTEN/AKT signaling pathway through competitively binding with hsa-miR-136-5p, hsa_circ_0006282 suppresses the growth of gastric cancer. [ABSTRACT FROM AUTHOR]

Growing studies have demonstrated that circRNAs (circular RNAs) act potential roles in tumor metastasis and progression. However, the expression and function of circ_0006404 in hepatocellular carcinoma (HCC) remain to be investigated. The expression of circ_0006404 and miR-624 was detected by qRT-PCR. CCK-8 assay, flow cytometry, and wound healing were performed to determine cell proliferation, cycle, and migration. The target of circ_0006404 was studied by bioinformatics and luciferase activity analysis. Our data indicated that circ_0006404 was overexpressed in HCC specimens and cells and ectopic expression of circ_0006404 increased HCC cell growth, cycle, and migration. Moreover, we showed that miR-624 was downregulated in HCC specimens and cells and miR-624 expression was negatively correlated with circ_0006404 expression in HCC specimens. Circ_0006404 sponged miR-624 in HCC cell, and the overexpression of circ_0006404 suppressed miR-624 expression in HCC cell. Furthermore, circ_0006404 induced HCC cell growth, cycle, and migration via regulating miR-624. These results elucidated that circ_0006404 facilitated HCC progression and might act as one new biomarker for this carcinoma. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignant tumor with 25–50% of 5-year survival. There exist urgent needs for the identification of novel biomarkers for the diagnostic and therapeutic strategies of cSCC. The differentially expressed circRNAs in cSCC tissues and non-lesional skin tissues were obtained through analyzing the circular RNAs (circRNAs) microarray dataset GSE74758. The expression pattern of the indicated circRNAs in cSCC tissues was confirmed by qRT-PCR. FISH analysis was used to detect the location of hsa_circ_0008234 in cells. RIP experiment was used to detect the interaction between hsa_circ_0008234 and miR-127-5p. CCK-8 analysis and colony formation assay were used to detect the proliferation of cSCC cells. qRT-PCR and western blot were adopted to detect the expression of ACDY7. Three differential expressed circRNAs were obtained from the microarray data (GSE74758), and hsa_circ_0008234 was confirmed to be highly expressed in cSCC tissues by qRT-PCR. Hsa_circ_0008234 was mainly located in cytoplasm and stable in cSCC cells. RIP experiment revealed that hsa_circ_0008234 directly interacts with miR-127-5p in cSCC cells. Hsa_circ_0008234 increased the cell viability and colony formation of cSCC cells through acting as the sponge of miR-127-5p. MiR-127-5p inhibited the expression of ADCY7 in cSCC cells through binding the 3'UTR of ADCY7. Hsa_circ_0008234 was positively associated with ADCY7 expression in cSCC tissues. Hsa_circ_0008234 facilitates the proliferation of cSCC through targeting miR-127-5p to regulate ADCY7 expression and has the potential to be a novel therapeutic target for cSCC. [ABSTRACT FROM AUTHOR]

Cerebral ischemia causes hypoxic injury and inflammation, and brain microvascular endothelial cells (BMVECs) dysfunction is an initial stage of blood-brain barrier disruption. Endothelial cells secrete extracellular vesicles (EVs) that are involved in intercellular signal transduction. EVs contain a variety of RNAs, proteins, and metabolites. Circular RNA (circRNA) is a member of the non-coding RNA. The expression profile and potential function of circRNAs in BMVECs are unknown. Here, human BMVECs have undergone hypoxia or TNF-α induction, and the changes in circRNAs were measured by RNA sequencing. A total of 70 circRNAs showed differential expression, including 43 previously unrecorded circRNAs and 27 recorded circRNAs. Since astrocyte end-feet encircle endothelial cells, they are considered the main targets of the EVs from BMVEC. The miRNA sequence data and bioinformatics were used to predict the circRNA-miRNA-mRNA networks in astrocytes. The gene ontology (GO) analysis showed the main downstream targets of circRNAs are DNA transcription regulation and protein kinase-related signaling pathways. These results suggest that altering circRNAs may be a potential therapeutic target for cerebral ischemia induced hypoxic injury and inflammation. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify different transcriptome expression profiles involved in the pathogenesis of diabetic nephropathy (DN) and to illustrate the diagnostic and therapeutic potential of mRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in DN progression. The participants were divided into four groups: normoalbuminuria (group DM), microalbuminuria (group A2), macroalbuminuria (group A3) and healthy controls (group N). There were three individuals in each group for sequencing. Transcriptome sequencing analysis was performed on the peripheral blood of all the participants to identify the differential expression of mRNAs, lncRNAs, and circRNAs between intervention groups and controls. The functional enrichment analysis, the short time-series expression miner (STEM) program, and the miRNA–circRNA–mRNA network were further conducted. To verify the reproducibility of transcriptome sequencing, 10 and 30 blood samples were collected from the control and diseased groups, respectively. Four candidate biomarkers were selected from differentially expressed circRNAs (circ_0005379, circ_0002024, and circ_0000567, and circ_0001017) and their concentrations in the blood were measured using quantitative PCR (qPCR). In the comparison of A2 with N, 549 mRNAs, 1259 lncRNAs, and 12 circRNAs were screened. In the comparison of A3 with N, 1217 mRNAs, 1613 lncRNAs, and 24 circRNAs were screened. Moreover, in the comparison of diabetes mellitus (DM) with N, 948 mRNAs, 1495 lncRNAs, and 25 circRNAs were screened. Functional enrichment analysis showed that differentially expressed mRNAs were related to insulin secretion, insulin resistance, and inflammation, while differentially expressed lncRNAs were mainly associated with crossover junction endodeoxyribonuclease activity. In STEM analysis, a total of 481 mRNAs and 152 differential expression circRNAs showed a significant tendency. The key relationships in the miRNA–circRNA–mRNA network were identified, such as hsa-miR-103a-3p-circ_0005379-PTEN, hsa-miR-497-5p-circ_0002024-IGF1R and hsa-miR-1269a-circ_0000567-SOX6. In addition, qPCR showed consistent results with RNA sequencing. We found that differentially expressed mRNAs, lncRNAs, and circRNAs participated in DN development. Circ_0005379, circ_0002024, and circ_0000567 could be adopted as potential biomarkers for DN. [ABSTRACT FROM AUTHOR]

CRC is the third most common cancer occurring worldwide and the second leading cause of cancer deaths. In the year 2020, 1,931,590 new cases of CRC and 935,173 deaths were reported. The last two decades have witnessed an intensive study of noncoding RNAs and their implications in various pathological conditions including cancer. Noncoding RNAs such as miRNAs, tsRNAs, piRNAs, lncRNAs, pseudogenes, and circRNAs have emerged as promising prognostic and diagnostic biomarkers in preclinical studies of cancer. Some of these noncoding RNAs have also been shown as promising therapeutic targets for cancer treatment. In this review, we have discussed the emerging roles of various types of noncoding RNAs in CRC and their future implications in colorectal cancer management and research. [ABSTRACT FROM AUTHOR]

CircRNAs is a novel type of endogenous RNA molecule that is produced from pre-mRNA without 5′cap and a tail of 3′polyA. It characterized by the presence of a covalent bond to form closed-loop structure. Recently, circRNAs have been identified in many species ranging from humans and animals to plants. It has several traits, such as evolutionary conservation, high stability, cell or tissue-specific expression, high abundance and so on, suggesting their potential biological significance. Current studies confirmed that circRNAs exert their functions in numerous ways including regulating the gene expression and protein translation, regulating other RNA transcripts by sponging miRNAs and proteins, and translating functional proteins or peptides and so on. This review summarized circRNAs molecular characteristics, biogenesis mechanism, prediction tools, database resources, main biological function of circRNAs, and research progresses of circRNAs in aquaculture. Our study provides the certain theoretical basis and reference for the researching the mechanism of circRNAs on aquaculture economic traits and vital functions in fish development, and providing novel techniques for aquaculture breeding in future. [ABSTRACT FROM AUTHOR]

Metastasis is the main culprit of cancer-associated mortality and involves a complex and multistage process termed the metastatic cascade, which requires tumor cells to detach from the primary site, intravasate, disseminate in the circulation, extravasate, adapt to the foreign microenvironment, and form organ-specific colonization. Each of these processes has been already studied extensively for molecular mechanisms focused mainly on protein-coding genes. Recently, increasing evidence is pointing towards RNAs without coding potential for proteins, referred to as non-coding RNAs, as regulators in shaping cellular activity. Since those first reports, the detection and characterization of non-coding RNA have explosively thrived and greatly enriched the understanding of the molecular regulatory networks in metastasis. Moreover, a comprehensive description of ncRNA dysregulation will provide new insights into novel tools for the early detection and treatment of metastatic cancer. In this review, we focus on discussion of the emerging role of ncRNAs in governing cancer metastasis and describe step by step how ncRNAs impinge on cancer metastasis. In particular, we highlight the diagnostic and therapeutic applications of ncRNAs in metastatic cancer. [ABSTRACT FROM AUTHOR]

With the rapid development of sequencing technology, scientists have been able to study and acquire a better understanding of non-coding RNAs (ncRNAs). Circular RNAs (circRNAs), a unique class of ncRNAs with a special loop structure, have been found to possess modulatory properties with respect to various biological processes, such as interacting with nucleic acids or proteins. In addition to their tissue-specific expression and high conservation across species, circRNAs are abundant and dynamically expressed in the nervous system, especially in nerve synapse, indicating their potential regulation in synaptic plasticity or neuronal disorders. In this review, we discuss the characteristics of circRNAs and their common biological functions, as well as their significant role in neurodevelopment, drug addiction and neurodegenerative diseases, aiming to guide further disease diagnoses and efficient therapy. [ABSTRACT FROM AUTHOR]

Recent researches reported that several circular RNAs (circRNAs) were associated with the glioblastoma (GBM) progression, while the regulatory role of circPITX1 remains unknown in GBM. The real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify circPITX1, miR-584-5p, and karyopherin b1 (KPNB1) expression in GBM tissues and cells. The proliferation capability of cells was analyzed by Cell Counting Kit-8 (CCK-8) and colony-forming assays. The matrigel angiogenesis assay was used to assess tube formation in GBM cells. Flow cytometry assays were conducted to evaluate the cell cycle distribution of GBM cells. The migration and invasion assays were assessed by transwell assay. The Western blot assay was employed to quantify the protein expression level in GBM tissues and cells. The targets of circPITX1 and miR-584-5p were confirmed by dual-luciferase reporter and RNA pull-down assays. A xenograft experiment in nude mice was used to assess the functional role of circPITX1 in vivo. CircPITX1 was obviously overexpressed in GBM tissues and cells when compared with negative groups. The functional experiment implied that knockdown of circPITX1 suppressed proliferation, angiogenesis, migration, invasion, and tumor growth in vivo along with induced cell cycle arrest of GBM cells. Furthermore, miR-584-5p was a target gene of circPITX1, and knockdown of miR-584-5p could abolish circPITX1 silencing-induced effects on GBM cells. KPNB1 was a target gene of miR-584-5p, and functional experiments revealed that overexpression of miR-584-5p repressed proliferation, angiogenesis, migration, invasion, and cell cycle process in GBM cells by targeting KPNB1. Mechanistically, circPITX1/miR-584-5p/KPNB1 axis regulated GBM process via mediating proliferation, angiogenesis, migration, invasion, and cell cycle process of GBM cells. [ABSTRACT FROM AUTHOR]

Soybean oil is composed of fatty acids and glycerol. The content and composition of fatty acids partly determine the quality of soybean seeds. Circular RNAs (circRNAs) are endogenous non-coding RNAs that competitively bind to microRNAs (miRNAs) through miRNA recognition elements, thereby acting as sponges to regulate the expression of target genes. Although circRNAs have been identified previously in soybean, only their expression has been investigated without exploration of the competitive endogenous RNAs (ceRNAs) network of circRNAs-miRNAs-mRNAs. In this study, circRNAs in immature pods of a low linolenic acid soybean Mutant 72' (MT72) and the wild-type control 'Jinong 18' (JN18) were systematically identified and analyzed at 30 and 40 days after flowering using high-throughput sequencing technology. We identified 6377 circRNAs, of which 114 were differentially expressed. Gene ontology and KEGG pathway analyses of targeted mRNAs in the ceRNAs network indicated that the differentially expressed circRNAs may be involved in fatty acid transport, suggesting that circRNAs may play a post-transcriptional regulatory role in soybean oil synthesis. This study provides a foundation for future exploration of the function of circRNAs in soybean and presents novel insights to guide further studies of plant circRNAs. [ABSTRACT FROM AUTHOR]

Exosomes, the nanoscale phospholipid bilayer vesicles, enriched in selected proteins, nucleic acids and lipids, which they participated in a variety of biological processes in the body, including physiology and pathology. CircRNAs (circular RNAs) are a class of single-stranded closed molecules with tissue development specific expression patterns that have crucial regulatory functions in various diseases. Non-coding RNAs (such as microRNAs and long non‑coding RNAs) in exosomes have also been shown to play an important regulatory role in humans. However, little research has focused on exosomal circRNAs. Recently, CircRNAs have been identified to be enriched and stably expressed in exosomes. In this review, we summarize the biogenesis and biological functions of exosomes and circRNA, and further revealed the potential role of exosome-derived circRNA in different diseases. Besides, we propose its use as a diagnostic marker and therapeutic punctuation for diseases, especially in cancer. [ABSTRACT FROM AUTHOR]

Mammalian brain presents extraordinary complexity reflected in the structure, function, and dynamic changes in the biological and physiological processes of development, maturity, and aging. Recent transcriptomic profiles from the brain tissues of distinct species have described a novel class of transcripts with a covalently closed-loop structure, called circular RNAs (circRNAs), which are produced by alternative back-splicing and derived from genes associated with synaptogenesis and neural activities. Brain is a tightly regulated and largely unexplored organ where circRNAs are highly enriched and expressed in the cell type-, spatiotemporal-specific, sex-biased, and age‐related manner. Although the biological functions of most of the circRNAs in the brain remain elusive, increased evidence suggests that dynamic changes in circRNA expression are critical for brain function and the maintenance of physiological homeostasis in the brain. Here, we review the latest immense progresses in the understanding of circRNA expression and function in the mammalian brain. We also discuss possibly biological functions of circRNAs in the brain, which may provide new sights of understanding brain development and aging, as well as the pathogenesis of mental diseases. [ABSTRACT FROM AUTHOR]

Background: Centromeres are specialized chromosomal domains involved in kinetochore formation and faithful chromosome segregation. Despite a high level of functional conservation, centromeres are not identified by DNA sequences, but by epigenetic means. Universally, centromeres are typically formed on highly repetitive DNA, which were previously considered to be silent. However, recent studies have shown that transcription occurs in this region, known as centromeric-derived RNAs (cenRNAs). CenRNAs that contribute to fundamental aspects of centromere function have been recently investigated in detail. However, the distribution, behavior and contributions of centromeric transcripts are still poorly understood. Objective: The aim of this article is to provide an overview of the roles of cenRNAs in centromere formation and function. Methods: We describe the structure and DNA sequence of centromere from yeast to human. In addition, we briefly introduce the roles of cenRNAs in centromere formation and function, kinetochore structure, accurate chromosome segregation, and pericentromeric heterochromatin assembly. Centromeric circular RNAs (circRNAs) and R-loops are rising stars in centromere function. CircRNAs have been successfully identified in various species with the assistance of high-throughput sequencing and novel computational approaches for non-polyadenylated RNA transcripts. Centromeric R-loops can be identified by the single-strand DNA ligation-based library preparation technique. But the molecular features and function of these centromeric R-loops and circRNAs are still being investigated. Conclusion: In this review, we summarize recent findings on the epigenetic regulation of cenRNAs across species, which would provide useful information about cenRNAs and interesting hints for further studies. [ABSTRACT FROM AUTHOR]

As a special type of noncoding RNA, circular RNAs (circRNAs) are prevalent in many organisms. They can serve as sponges for microRNAs and protein scaffolds, or templates for protein translation, making them linked to cellular homeostasis and disease progression. In recent years, circRNAs have been found to be abnormally expressed during the processes of viral infection and pathogenesis, and can help a virus escape the immune response of a host. Thus, they are now considered to play important functions in the invasion and development of viruses. Moreover, the potential application of circRNAs as biomarkers of viral infection or candidates for therapeutic targeting deserves consideration. This review summarizes circRNAs in the transcriptome, including their classification, production, functions, and value as biomarkers. This review paper also describes research progress on circRNAs in viral infection (mainly hepatitis B virus, HIV, and some human herpes viruses) and aims to provide new ideas for antiviral therapies targeting circRNAs. [ABSTRACT FROM AUTHOR]

Adipose-derived mesenchymal stem cells (ADSCs) are considered to be seed cells in bone tissue engineering and emerging evidence indicates that circular RNAs (circRNAs) function in the osteogenic differentiation of ADSCs. The mechanisms of osteoblastic differentiation of ADSCs from the perspective of circRNA modulation are examined in this study. First, circRNA-23525 was upregulated during osteoblastic differentiation of ADSCs. Second, overexpression of circRNA-23525 increased Runx2, ALP and OCN at both mRNA and protein levels. Alkaline phosphatase (ALP) and Alizarin Red staining indicated a similar tendency. Silencing circRNA-23525 produced the opposite effect. Bioinformatics analysis with luciferase assays confirmed that circRNA-23525 functioned as a sponge for miR-30a-3p. In the osteoblastic differentiation of ADSCs, the dynamic expression of miR-30a-3p and circRNA-23525 resulted in an opposite trend at 3, 7 and 14 days. Overexpression of circRNA-23525 downregulated miR-30a-3p and knockdown of circRNA-23525 promoted the expression of miR-30a-3p. Bioinformatics methods and luciferase assays suggested that miR-30a-3p modulated Runx2 expression by targeting 3′UTR. Knockdown of miR-30a-3p facilitated osteogenesis in ADSCs and enhancing miR-30a-3p interfered with the osteogenic process. Finally, circRNA-23525 overexpression significantly increased Runx2 expression, while co-transfection of miR-30a-3p mimics reversed it. Runx2 expression was decreased in circRNA-23525-knockdown ADSCs but expression was rescued by including the miR-30a-3p inhibitor in the osteoblastic process. ALP activity and mineralized bone matrix confirmed the function of circRNA-23525/miR-30a-3p in osteogenesis. Taken together, the current study demonstrated that circRNA-23525 regulates Runx2 expression via targeting miR-30a-3p and is thus a positive regulator in the osteoblastic differentiation of ADSCs. [ABSTRACT FROM AUTHOR]