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miRNAs are crucial regulators in a variety of physiological and pathological processes, while their regulation mechanisms were usually described as negatively regulating gene expression by targeting the 3'-untranslated region(3'-UTR) of target gene miRNAs through seed sequence in tremendous studies. However, recent evidence indicated the existence of non-canonical mechanisms mediated by binding other molecules besides mRNAs. Additionally, accumulating evidence showed that functions of intracellular and intercellular miRNAs exhibited spatiotemporal patterns. Considering that detailed knowledge of the miRNA regulating mechanism is essential for understanding the roles and further clinical applications associated with their dysfunction and dysregulation, which is complicated and not fully clarified. Based on that, we summarized the recently reported regulation mechanisms of miRNAs, including recognitions, patterns of actions, and chemical modifications. And we also highlight the novel findings of miRNAs in atherosclerosis progression researches to provide new insights for non-coding RNA-based therapy in intractable diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Colorectal cancer (CRC) has been recorded amongst the most common cancers in the world, with high morbidity and mortality rates, and relatively low survival rates. With risk factors such as chronic illness, age, and lifestyle associated with the development of CRC, the incidence of CRC is increasing each year. Thus, the discovery of novel biomarkers to improve the diagnosis and prognosis of CRC has become beneficial. Long non-coding RNAs (lncRNAs) have been emerging as potential players in several tumor types, one among them is the lncRNA H19. The paternally imprinted oncofetal gene is expressed in the embryo, downregulated at birth, and reappears in tumors. H19 aids in CRC cell growth, proliferation, invasion, and metastasis via various mechanisms of action, significantly through the lncRNA-microRNA (miRNA)-messenger RNA (mRNA)-competitive endogenous RNA (ceRNA) network, where H19 behaves as a miRNA sponge. The RNA transcript of H19 obtained from the first exon of the H19 gene, miRNA-675 also promotes CRC carcinogenesis. Overexpression of H19 in malignant tissues compared to adjacent non-malignant tissues marks H19 as an independent prognostic marker in CRC. Besides its prognostic value, H19 serves as a promising target for therapy in CRC treatment., (Copyright ©2023, Yale Journal of Biology and Medicine.)

Exosomes are a novel and promising drug delivery platform because of their endogenous origin, stability, biocompatibility, and other unique features. As the efficient loading and delivery of long RNA to target cells for therapeutic purposes remains challenging, a new exosome‐based RNA delivery system is proposed using a controllable RNA enrichment and releasing protocol. The system employs RNA aptamer–protein interactions and reversible light‐inducible protein–protein interaction modules by remolding exosome producer cells. Endogenous microRNA 21 (miR‐21) sponges, inhibitors of miR‐21, are successfully enriched on the plasma membrane and are sorted into exosomes by the biogenesis of the exosomes. The loading capacity of miR‐21 sponges is enhanced by 14‐fold in the light‐inducible loading system. In addition, targeted delivery of miR‐21 to leukemia cells is achieved by modifying exosomes with the cholesterol‐conjugated aptamer AS1411, resulting in significant cell apoptosis by blocking the function of miR‐21 in leukemia cells. This work provides an exosome‐based light‐inducible vehicle to efficiently load and deliver long endogenous RNA, which can enable more RNA‐based therapeutics for personalized cancer medicine.Exosomes are a novel and promising method for drug delivery. Here, a new exosome‐based light‐inducible vehicle is constructed through multiple molecular engineering and a blue light controllable RNA enrichment/releasing protocol. This system can efficiently load and deliver a long endogenous miRNA‐based agent (such as miRNA‐21 sponges) to target tumor cells, and thus regulate the expression of target protein of miRNA. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA)-mediated crosstalk between coding and non-coding RNAs of various types is known as the competing endogenous RNA (ceRNA) concept. Here, we propose that there is a specific variant of the ceRNA language that takes advantage of simple sequence repeat (SSR) wording. We applied bioinformatics tools to identify human transcripts that may be regarded as repeat-associated ceRNAs (raceRNAs). Multiple protein-coding transcripts, transcribed pseudogenes, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) showing this potential were identified, and numerous miRNAs were predicted to bind to SSRs. We propose that simple repeats expanded in various hereditary neurological diseases may act as sponges for miRNAs containing complementary repeats that would affect raceRNA crosstalk. Based on the representation of specific SSRs in transcripts, expression data for SSR-binding miRNAs and expression profiling data from patients, we determined that raceRNA crosstalk is most likely to be perturbed in the case of myotonic dystrophy type 1 (DM1) and type 2 (DM2). [ABSTRACT FROM AUTHOR]

Abstract Circular RNAs (circRNAs), a large novel type of endogenous transcripts, have become a new research hotspot in the field of RNA biology. CircRNAs are mainly generated from exons or introns via multiple mechanisms, and the majority of circRNAs are stable and conserved across different species. Recent studies have revealed that circRNAs can function as miRNA sponges, binding partners of proteins, regulators of transcription, or can even be translated into proteins. Growing evidence has demonstrated that circRNAs play important roles in a wide variety of biological processes such as cell proliferation, apoptosis and senescence, and may serve as potential diagnostic biomarkers or therapeutic targets for various cardiovascular diseases. Here, we review the biogenesis, properties and biological function of circRNAs, and summarize their roles in cardiovascular disorders. Highlights • circRNAs are a novel class of RNA molecules that form covalently closed loops. • circRNAs are formed by back-splicing. • circRNAs may regulate gene expression through multiple mechanisms. • circRNAs are involved in the pathogenesis of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that circular RNAs (circRNAs) play critical roles in carcinomas. However, the contributions of circRNAs to breast cancer remain unclear. Herein, we determined the role of circZNF609 in breast cancer.Methods: A total of 143 breast cancer and 38 normal tissues were collected to assess the expression of circZNF609 and its relationship with breast cancer prognosis. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of circZNF609 in breast cancer progression and its underlying molecular mechanisms.Results: CircZNF609 was markedly over-expressed in breast cancer tissues and cell lines, and high circZNF609 expression was closely associated with poor outcome. Silencing of circZNF609 inhibited the malignant phenotype of breast cancer in vitro and in vivo. Mechanistically, circZNF609 served as a sponge of miR-145-5p to elevate p70S6K1 expression. Moreover, miR-145-5p overexpression or p70S6K1 knockdown abrogated the oncogenic effects of circZNF609 in breast cancer. In addition, clinically, a strong negative correlation was observed between the expression of circZNF609 and miR-145-5p in breast cancer tissues (r=–0.597, P<0.001), whereas a positive correlation between circZNF609 and p70S6K1 expression (r=0.319, P<0.001).Conclusion: These data suggest that circZNF609 contributes to breast cancer progression, at least partly, by modulating the miR-145-5p/p70S6K1 axis, and it may be a potential therapeutic target for breast cancer. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a large class of endogenously expressed non-coding RNAs formed by covalently closed loops through back-splicing. High throughput sequencing technologies have identified thousands of circRNAs with high sequence conservation and cell type specific expression in eukaryotes. CircRNAs play multiple important roles in cellular physiology functioning as miRNA sponges, transcriptional regulators, RBP binding molecules, templates for protein translation, and immune regulators. In a clinical context, circRNAs expression is correlated with patient’s clinicopathological features in cancers including breast, liver, gastric, colorectal, and lung cancer. Additionally, distinct properties of circRNAs, such as high stability, exonuclease resistance, and existence in body fluids, show promising role for circRNAs as molecular biomarkers for tumor diagnosis, non-invasive monitoring, prognosis, and therapeutic intervention. Therefore, it is critical to further understand the molecular mechanism underlying circRNAs interaction in tumors and the recent progress of this RNA species in cancer development. In this review, we provide a detailed description of biological functions, molecular role of circRNAs in different cancers, and its potential role as biomarkers in a clinical context. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the most common solid tumors in women involving multiple subtypes. However, the mechanism for subtypes of breast cancer is still complicated and unclear. Recently, several studies indicated that long non-coding RNAs (lncRNAs) could act as sponges to compete miRNAs with mRNAs, participating in various biological processes.Methods: We concentrated on the competing interactions between lncRNAs and mRNAs in four subtypes of breast cancer (basal-like, HER2+, luminal A and luminal B), and analyzed the impacts of competing endogenous RNAs (ceRNAs) on each subtype systematically. We constructed four breast cancer subtype-related lncRNA-mRNA ceRNA networks by integrating the miRNA target information and the expression data of lncRNAs, miRNAs and mRNAs.Results: We constructed the ceRNA network for each breast cancer subtype. Functional analysis revealed that the subtype-related ceRNA networks were enriched in cancer-related pathways in KEGG, such as pathways in cancer, miRNAs in cancer, and PI3k-Akt signaling pathway. In addition, we found three common lncRNAs across the four subtype-related ceRNA networks, NEAT1, OPI5-AS1 and AC008124.1, which played specific roles in each subtype through competing with diverse mRNAs. Finally, the potential drugs for treatment of basal-like subtype could be predicted through reversing the differentially expressed lncRNA in the ceRNA network.Conclusion: This study provided a novel perspective of lncRNA-involved ceRNA network to dissect the molecular mechanism for breast cancer. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have been verified to participate in various types of malignant tumors, including osteosarcoma (OS), which is the most common primary bone tumor with outstanding morbidity. Although an increasing number of lncRNAs have been reported to mediate the occurrence of OS, the potential mechanisms are still unclear. This study intends to uncover the mechanism by which lncRNA LINC01133 functions as an miRNA sponge to mediate OS tumorigenicity. In this study, we found that the expression level of LINC01133 was statistically upregulated in OS tumor tissue and cell lines compared to noncancerous tissues and a normal human osteoplastic cell line. LINC01133 silencing could also observably suppress the proliferation, migration, and invasion of OS cells (HOS and U2-OS). Bioinformatics analysis predicted that LINC01133 specifically targeted miR-422a, which was validated by dual-luciferase reporter assay. Furthermore, functional experiments revealed that miR-422a played a tumor-suppressive role in OS progression and could effectively reverse the function of LINC01133. In summary, our study discovered that lncRNA LINC01133 aggravates the proliferation, migration, and invasion of OS by sponging miR-422a, which provides a novel insight in the tumorigenesis of OS. [ABSTRACT FROM AUTHOR]

CircRNA is a type of closed circular non-coding RNA formed by reverse splicing and plays an important role in regulating the growth and development of plants and animals. To investigate the function of circ-FoxO3 in mouse myoblast cells’ (C2C12) differentiation and proliferation, we used RT-qPCR to detect the expression level of circ-FoxO3 in mouse myoblast cells at different densities and different differentiation stages, and the specific interference fragment was used to inhibit the expression level of circ-FoxO3 in myoblast cells to observe its effect on myoblast cells proliferation and differentiation. We found that the expression level of circ-FoxO3 in myoblast cells increased with the prolongation of myoblast cells differentiation time, and its expression level decreased with the proliferation of myoblast cells. At the same time, we found that the differentiation ability of the cells was significantly increased (p < 0.05), but the cell proliferation was unchanged (p > 0.05) after inhibiting the expression of circ-FoxO3 in myoblast cells. Combining the results of bioinformatics analysis and the dual luciferase reporter experiment, we found that circ-FoxO3 is a sponge of miR-138-5p, which regulates muscle differentiation. Our study shows that circ-FoxO3 can inhibit the differentiation of C2C12 myoblast cells and lay a scientific foundation for further study of skeletal muscle development at circRNA levels.

Circular RNAs (circRNAs) have been found to be highly abundant and evolutionarily conserved in both animals and plants. Tomato is a widely characterized model plant, but very little information is available about the feature and functions of circRNAs in this species. In the present study, to invest whether circRNAs are involved in fruit ripening process, we used deep sequencing to monitor the changes in circRNAs between mature green tomato fruit and red ripening ones. A total of 705 circRNAs were detected in these two samples, of which 340 were differentially regulated. CircRNAs were reported to function as cis -regulator and miRNA sponge to regulate physiological and biochemical metabolism in animals. In this study, 19 differentially expressed circRNAs were found to function as putative miRNA sponges to regulate the expression of 94 target mRNAs. Furthermore, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation of both parent genes and target mRNAs were performed to reveal the functions of differentially expressed circRNAs during ripening. The results revealed that circRNAs may be involved in regulating fruit ripening by mediating metabolism adaptation, hormone balance, and photosynthesis related pathways. Besides, circRNAs were predicted to be involved in transcription regulation through targeting transcription factors such as ethylene-responsive transcription factor (ERF), squamosa promoter binding-like protein (SBP) and myeloblastosis (MYB) proto-oncogene protein. These results shed light on the role of circRNAs in fruit ripening and help to identify novel circRNAs in tomato. [ABSTRACT FROM AUTHOR]

Circular RNA (circRNA) generated by alternative splicing represents a special class of non-coding RNA molecule. CircRNAs are abundant in the eukaryotic cell cytoplasm and have a characteristic organization, timing of action and disease specificity. In contrast to linear RNA, circRNAs are resistant to RNA exonuclease. Consequently, circRNA escapes normal RNA turnover and this improves circRNA stability. CircRNAs can be degraded by microRNA (miRNA) and this results in linearization of the circRNA, which can then act as competitor to endogenous RNA. Through interactions with disease-related miRNA, circRNA can play an important regulatory role in specific diseases. Furthermore, circRNAs have significant potential to become new clinical diagnostic markers. [ABSTRACT FROM PUBLISHER]

Representing a novel type of endogenous noncoding RNAs, circular RNAs (circRNAs) have recently gained much attention for their involvement in multiple biological processes. CircRNAs are ubiquitously expressed in eukaryotic cells and modulate gene expression by acting as sponges of microRNAs (miRNAs) or other proteins, such as RNA-binding proteins (RBPs). Due to their unique structure, circRNAs are more stable than linear RNAs. Expression profiles of circRNAs are associated with clinicopathological characteristics of colorectal cancer patients, such as differentiation, TNM classification and distant metastasis. Furthermore, circRNAs play crucial roles in multiple processes associated with malignant phenotypes, including cell proliferation/cycle, apoptosis and invasion. Improvements in RNA-sequencing methods have helped researchers to elucidate molecular interactions between circRNAs and colorectal cancer. This review provides a comprehensive overview of the features and functions of circRNAs, as well as insights into their roles in the onset and development of colorectal cancer. Combined with the reported results, the identification of circRNAs associated with colorectal cancer will certainly contribute to early detection and help to design treatment strategies for colorectal cancer. Screening for circRNAs may provide an accessible, noninvasive yet highly sensitive diagnosis for colorectal cancer. Furthermore, a better understanding of the roles of circRNAs may also provide a novel predictive feature in colorectal cancer therapy and prognosis. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNAs) is post-transcriptional regulator of mRNA. However, the prevalence and activity of miRNA are regulated by other regulators. miRNA inhibitors are natural or artificial RNA transcripts that sequestrate miRNAs and decrease or even eliminate miRNA activity. Competing endogenous RNAs (ceRNAs) are natural and intracellular miRNA inhibitors that compete to bind to shared miRNA recognition elements (MREs) to decrease microRNA availability and relieve the repression of target RNAs. In recent years, studies have revealed that ceRNA crosstalk is involved in many pathophysiological processes and adds a new dimension to miRNA regulation. Artificial miRNA inhibitors are RNA transcripts that are synthesized via chemical and genetic methods. Artificial miRNA inhibitors can be used in miRNA loss-of-function research and gene therapies for certain diseases. In this review, we summarize the recent advances in the two different types of miRNA inhibitors. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have been proved as important regulators in many diseases, including cancers. HOXA11 antisense RNA (HOXA11-AS) is a novel identified lncRNA associated with cancer progression. However, the role of HOXA11-AS in glioma remains poorly understood and needs to be elucidated. The purpose of this study is to investigate the role and regulating mechanism of HOXA11-AS on gliomagenesis. Expression of HOXA11-AS was significantly upregulated in glioma tissue and cell lines compared with the adjacent normal tissue and cells. Moreover, patients with high HOXA11-AS expression had a shorter survival and poorer prognosis than that of lower expression. Loss-of-function experiments revealed that HOXA11-AS knockdown inhibited the proliferation, induced cell cycle arrest at G0/G1 phase, and enhanced the apoptosis. Bioinformatics prediction forecast that miR-140-5p directly targeted HOXA11-AS at 3′-UTR, which was confirmed by luciferase reporter assay. In vitro rescue experiment assays, miR-140-5p inhibitor transfection, could reverse the function of HOXA11-AS knockdown on the proliferation, cell cycle arrest, and apoptosis. Taken together, the present study illustrates that the pathway of HOXA11-AS sponging miR-140-5p might play a vital regulating role in the development and progression of glioma. [ABSTRACT FROM AUTHOR]

Insights into the circular RNA (circRNA) exploration have revealed that they are abundant in eukaryotic transcriptomes. Diverse genomic regions can generate different types of RNA circles, implying their diversity. Covalently closed loop structures elevate the stability of this new type of noncoding RNA. High-throughput sequencing analyses suggest that circRNAs exhibit tissue- and developmental-specific expression, indicating that they may play crucial roles in multiple cellular processes. Strikingly, several circRNAs could function as microRNA sponges and regulate gene transcription, highlighting a new class of important regulators. Here, we review the recent advances in knowledge of endogenous circRNA biogenesis, properties and functions. We further discuss the current findings about circRNAs in human diseases. In plants, the roles of circRNAs remain a mystery. Online resources and bioinformatics identification of circRNAs are essential for the analysis of circRNA biology, although different strategies yield divergent results. The understanding of circRNA functions remains limited; however, circRNAs are enriching the RNA world, acting as an emerging key player. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a type of non-coding RNA molecules that lack a 5'-terminal cap and 3'-terminal poly A tail. A large number of circRNAs have been identified through biological experiments, computational methods and high-throughput sequencing. CircRNA sequence composition determines if a given circRNA is exonic, intronic or retained-intronic. CircRNAs are more abundant and stable than linear mRNAs, and their expression is both step- and location-specific. CircRNAs mediate transcriptional and post-transcriptional regulation of gene and protein expression. CircRNAs regulate cancer development via multiple mechanisms, including miRNA sponges, modulating Wnt signaling pathway and epithelial-mesenchymal transition. An in-depth study of circRNA will provide a better understanding of carcinogenesis and assist in developing clinical diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: MicroRNA (miRNA) sponges with multiple tandem miRNA binding sequences can sequester miRNAs from their endogenous target mRNAs. Therefore, miRNA sponge acting as a decoy is extremely important for long-term lossof- function studies both in vivo and in silico. Recently, a growing number of in silico methods have been used as an effective technique to generate hypotheses for in vivo methods for studying the biological functions and regulatory mechanisms of miRNA sponges. However, most existing in silico methods only focus on studying miRNA sponge interactions or networks in cancer, the module-level properties of miRNA sponges in cancer is still largely unknown. Results: We propose a novel in silico method, called miRSM (miRNA Sponge Module) to infer miRNA sponge modules in breast cancer. We apply miRSM to the breast invasive carcinoma (BRCA) dataset provided by The Cancer Genome Altas (TCGA), and make functional validation of the computational results. We discover that most miRNA sponge interactions are module-conserved across two modules, and a minority of miRNA sponge interactions are module-specific, existing only in a single module. Through functional annotation and differential expression analysis, we also find that the modules discovered using miRSM are functional miRNA sponge modules associated with BRCA. Moreover, the module-specific miRNA sponge interactions among miRNA sponge modules may be involved in the progression and development of BRCA. Our experimental results show that miRSM is comparable to the benchmark methods in recovering experimentally confirmed miRNA sponge interactions, and miRSM outperforms the benchmark methods in identifying interactions that are related to breast cancer. Conclusions: Altogether, the functional validation results demonstrate that miRSM is a promising method to identify miRNA sponge modules and interactions, and may provide new insights for understanding the roles of miRNA sponges in cancer progression and development [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a large type of noncoding RNAs characterized by their circular shape resulting from covalently closed continuous loops. They are known to regulate gene expression in mammals. These tissue-specific transcripts are largely generated from exonic or intronic sequences of their host genes. Although several models of circRNA biogenesis have been proposed, the understanding of their origin is far from complete. Unlike other noncoding RNAs, circRNAs are widely expressed, highly conserved and stable in cytoplasm, which confer special functionalities to them. They are known to serve as microRNA (miRNA) sponges, regulators of alternative splicing, transcription factors and encode for proteins. The expression of circRNAs is associated with several pathological states and may potentially serve as novel diagnostic or predictive biomarkers. CircRNAs are known to regulate the expression of numerous cancer-related miRNAs. The circRNA-miRNA-mRNA axis is a known regulatory pattern of several cancer-associated pathways, with both agonist and antagonist effects on carcinogenesis. In consideration of their potential clinical relevance, circRNAs are at the center of ongoing research initiatives on cancer prevention and treatment. In this review, we discuss the current understanding of circRNAs and the prospects for their potential clinical application in the management of cancer patients. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) belong to the genre of long non-coding RNAs that are formed by special back-splicing events and are currently the molecule of interest for studies globally due their involvement in various ailments like diabetes, neurodegenerative disorders, cardio-vascular diseases and cancers. These class of highly stable RNAs participate in diverse cellular functionalities including microRNA (miRNA) sponging, ceRNA (competing endogenous RNA) activity or via exhibiting RNA binding protein (RBP) interactions. They are also known to regulate cancer progression both positively and negatively through various biological pathways such as, modulating the cell cycle and apoptotic pathways, epigenetic regulation, and translational and/or transcriptional regulations etc. Given its significance, a variety of computational tools and dedicated databases have been created for the identification, quantification, and differential expression of such RNAs in combination with sequencing approaches. In this review, we provide a comprehensive analysis of the numerous computational tools, pipelines, and online resources developed in recent years for the detection and annotation of circRNAs. We also summarise the most recent findings regarding the characteristics, functions, biological processes, and involvement of circRNAs in diseases. The review emphasises the significance of circRNAs as potential disease biomarkers and new treatment targets. • Current status and future viewpoints of circRNA research are discussed. • Significant role of circRNAs in cancer and non cancer disease were analysed. • Systematic review of tools and databases dedicated to circRNA research. • Scope of CircRNA based biomarkers/ therapeutics are discussed. [ABSTRACT FROM AUTHOR]

Ocular neovascular disease (OND), characterized by the aberrant formation of immature blood vessels, is the leading cause of vision impairment and blindness. It is important to find effective ways to diagnose and treat these diseases. Circular RNA (circRNA) is a group of endogenous non-coding RNA that play a crucial role in regulating different biological processes. Due to their close association with ocular disease and angiogenesis, circRNAs have become a hotspot in OND research. In this review, we intensively investigate the possibility of using circRNAs in the management of ONDs. In general, angiogenesis is divided into five phases. On the basis of these five steps, we describe the potential of using circRNAs by introducing how they regulate angiogenesis. Subsequently, the interactions between circRNAs and ONDs, including pterygium, corneal neovascularization, age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, are analyzed in detail. We also introduce the potential use of circRNAs as OND diagnostic biomarkers. Finally, we summarize the prospects of using circRNAs as a potential strategy in OND management. The gaps in recent research are also pointed out with the purpose of promoting the introduction of circRNAs into clinical applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Osteosarcoma (OS) prevailing in children and adolescents mainly occurs at the metaphysis of long bones. As it is associated with a high invasive and metastatic ability, resistance to chemotherapy, and a low 5‑year survival rate, the diagnosis and treatment of OS post a global healthy issue. Over the past decades, RNA biology has shed new light onto the pathogenesis of OS. As a type of non‑coding RNAs, circular RNAs (circRNAs) have been found to play crucial roles in cellular activities. Recently, a large number of circRNAs have been identified in OS and some of them have been validated to be functional in OS. In the present review, abnormally expressed and different types of circRNAs in OS are summarized. Functional studies on circRNAs have revealed that circRNAs can regulate gene expression at different levels, such as gene transcription, precursor mRNA splicing, miRNA sponges and translation into proteins/peptides. Mechanistic analyses on circRNAs show that circRNAs can regulate JAK‑STAT3, NF‑κB, PI3K‑AKT, Wnt/β‑catenin signaling pathways during the occurrence and development of OS. Furthermore, the potential clinical applications of circRNAs are also emphasized. The present review focus on the current knowledge on the functions and mechanisms of circRNAs in the pathogenesis of OS, aiming to provide new insight into the OS diagnosis and treatment of OS.

Macrophages (Mφ) are long-lived myeloid cells that can polarize towards the proinflammatory M1 or proresolving M2 phenotype to control diverse biological processes such as inflammation, tissue damage, and regeneration. Noncoding RNA are a class of nonprotein-coding transcriptome with numerous interdependent biological roles; however, their functional interaction in the regulation of Mφ polarization and immune responses remain unclear. Here, we show antagonistic relationship between lncRNA (MALAT1) and microRNA (miR-30b) in shaping macrophage polarization and immune functions. MALAT1 expression displays a time-dependent induction during Mφ differentiation and, upon challenge with TLR4 agonist (E. coli LPS). MALAT1 knockdown promoted the expression of M2Mφ markers without affecting M1Mφ markers, suggesting that MALAT1 favors the M1 phenotype by suppressing M2 differentiation. Compared to the control, MALAT1 knockdown resulted in reduced antigen uptake and processing, bacterial phagocytosis, and bactericidal activity, strongly supporting its critical role in regulating innate immune functions in Mφ. Consistent with this, MALAT1 knockdown showed impaired cytokine secretion upon challenge with LPS. Importantly, MALAT1 exhibit an antagonistic expression pattern with all five members of the miR-30 family during M2 Mφ differentiation. Dual-luciferase assays validated a novel sequence on MALAT1 that interacts with miR-30b, a microRNA that promotes the M2 phenotype. Phagocytosis and antigen processing assays unequivocally demonstrated that MALAT1 and miR-30b are functionally antagonistic. Concurrent MALAT1 knockdown and miR-30b overexpression exhibited the most significant attenuation in both assays. In human subjects with periodontal disease and murine model of ligature-induced periodontitis, we observed higher levels of MALAT1, M1Mφ markers and downregulation of miR-30b expression in gingival tissues suggesting a pro-inflammatory function of MALAT1 in vivo . Overall, we unraveled the role of MALAT1 in Mφ polarization and delineated the underlying mechanism of its regulation by involving MALAT-1-driven miR-30b sequestration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ahmad, Naqvi, Valverde and Naqvi.)

Circular (circ)RNAs have emerged as novel regulators of gene expression through various mechanisms. However, most publications focus on functional circRNAs regulating target gene expression by interacting with micro (mi)RNAs and acting as competing endogenous RNAs (ceRNAs). Although the theory of miRNA sponging by ceRNAs suggests the inhibition of miRNA activity, many studies are biased toward the selection of miRNAs showing a reverse expression pattern compared with circRNA expression. Although several computational tools and molecular assays have been used to predict and validate the interaction of miRNAs with circRNAs, the actual validation of functional in vivo interactions needs careful consideration of molecular experiments with specific controls. As extensive research is being performed on circRNA, many questions arise on the functional significance of circRNA-miRNA interactions. We hope the critical discussion on the criteria for selecting circRNA-miRNA pairs for functional analysis and providing standard methods for validating circRNA-miRNA interactions will advance our understanding of circRNAs as novel gene regulators. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs Translation > Regulation RNA Methods > RNA Analyses in Cells., (© 2023 Wiley Periodicals LLC.)

CircRNAs are a class of endogenous long non-coding RNAs with a single-stranded circular structure. Most circRNAs are relatively stable, highly conserved, and specifically expressed in tissue during the cell and developmental stages. Many circRNAs have been discovered in OSCC. OSCC is one of the most severe and frequent forms of head and neck cancer today, with a poor prognosis and low overall survival rate. Due to its prevalence, OSCC is a global health concern, characterized by genetic and epigenomic changes. However, the mechanism remains vague. With the advancement of biotechnology, a large number of circRNAs have been discovered in mammalian cells. CircRNAs are dysregulated in OSCC tissues and thus associated with the clinicopathological characteristics and prognosis of OSCC patients. Research studies have demonstrated that circRNAs can serve as biomarkers for OSCC diagnosis and treatment. Here, we summarized the properties, functions, and biogenesis of circRNAs, focusing on the progress of current research on circRNAs in OSCC.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Both genetic and environmental factors through a multitude of underlying molecular mechanisms participate in the pathogenesis of HCC. Recently, numerous studies have shown that circular RNAs (circRNAs), an emerging class of non-coding RNAs characterized by the presence of covalent bonds linking 3' and 5' ends, play an important role in the initiation and progression of cancers, including HCC. In this review, we outline the current status of the field of circRNAs, with an emphasis on the functions and mechanisms of circRNAs in HCC and its microenvironment. We also summarize and discuss recent advances of circRNAs as biomarkers and therapeutic targets. These efforts are anticipated to throw new insights into future perspectives about circRNAs in basic, translational and clinical research, eventually advancing the diagnosis, prevention and treatment of HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rao, Peng, Tian, Fu and Zhang.)

Background: Abdominal fat deposition depends on both the proliferation of preadipocytes and their maturation into adipocytes, which is a well-orchestrated multistep process involving many regulatory molecules. Circular RNAs (circRNAs) have emergingly been implicated in mammalian adipogenesis. However, circRNA-mediated regulation in chicken adipogenesis remains unclear. Our previous circRNA sequencing data identified a differentially expressed novel circRNA, 8:27,886,180|27,889,657, during the adipogenic differentiation of chicken abdominal preadipocytes. This study aimed to investigate the regulatory role of circDOCK7 in the proliferation and adipogenic differentiation of chicken abdominal preadipocytes, and explore its molecular mechanisms of competing endogenous RNA underlying chicken adipogenesis., Results: Our results showed that 8:27,886,180|27,889,657 is an exonic circRNA derived from the head-to-tail splicing of exons 19-22 of the dedicator of cytokinesis 7 (DOCK7) gene, abbreviated as circDOCK7. CircDOCK7 is mainly distributed in the cytoplasm of chicken abdominal preadipocytes and is stable because of its RNase R resistance and longer half-life. CircDOCK7 is significantly upregulated in the abdominal fat tissues of fat chickens compared to lean chickens, and its expression gradually increases during the proliferation and adipogenic differentiation of chicken abdominal preadipocytes. Functionally, the gain- and loss-of-function experiments showed that circDOCK7 promoted proliferation, G0/G1- to S-phase progression, and glucose uptake capacity of chicken abdominal preadipocytes, in parallel with adipogenic differentiation characterized by remarkably increased intracellular lipid droplet accumulation and triglyceride and acetyl coenzyme A content in differentiated chicken abdominal preadipocytes. Mechanistically, a pull-down assay and a dual-luciferase reporter assay confirmed that circDOCK7 interacted with gga-miR-301b-3p, which was identified as an inhibitor of chicken abdominal adipogenesis. Moreover, the ACSL1 gene was demonstrated to be a direct target of gga-miR-301b-3p. Chicken ACSL1 protein is localized in the endoplasmic reticulum and mitochondria of chicken abdominal preadipocytes and acts as an adipogenesis accelerator. Rescue experiments showed that circDOCK7 could counteract the inhibitory effects of gga-miR-301b-3p on ACSL1 mRNA abundance as well as the proliferation and adipogenic differentiation of chicken abdominal preadipocytes., Conclusions: CircDOCK7 serves as a miRNA sponge that directly sequesters gga-miR-301b-3p away from the ACSL1 gene, thus augmenting adipogenesis in chickens. These findings may elucidate a new regulatory mechanism underlying abdominal fat deposition in chickens., (© 2023. The Author(s).)

Aims Overexpression of either member of the miR-199 family, miR-199a-5p, or miR-199b-5p (hereinafter referred to as miR-199a or miR-199b) promotes pathological cardiac hypertrophy, but little is known about the role of endogenous miR-199 in cardiac development and disease. Our study aimed to determine the physiological function of the endogenous miR-199 family in cardiac homeostasis maintenance. Methods and results We generated a sponge transgenic mouse model with a specific disruption of miR-199 in the heart. To our surprise, we found that knockdown of endogenous miR-199 caused physiological cardiac hypertrophy characterized by an increased heart weight and cardiomyocyte size, but with normal cardiac morphology and function. Furthermore, we also identified PGC1a as the target gene of the miR-199 family, and PGC1a was also increased in sponge transgenic mice. Conclusion Inhibition of endogenous miR-199 led to physiological cardiac hypertrophy probably due to the up-regulation of PGC1a, uncovering a surprising role for endogenous miR-199 in the maintenance of cardiac homeostasis. [ABSTRACT FROM AUTHOR]