microRNA Sponges Research Articles

Exploring the molecular biomarker utility of circCCT3 in multiple myeloma: A favorable prognostic indicator, particularly for R-ISS II patients.

Circular RNAs (circRNAs) are associated with the pathobiology of multiple myeloma (MM). Recent findings regarding circCCT3 support its involvement in the development and progression of MM, through microRNA sponging. Thus, we aimed to examine the expression of circCCT3 in smoldering and symptomatic MM and to assess its clinical importance. Three cell lines from plasma cell neoplasms were cultured and bone marrow aspirate (BMA) samples were collected from 145 patients with MM or smoldering MM. Next, CD138+ enrichment was performed in BMA samples, followed by total RNA extraction and reverse transcription. Preamplification of circCCT3 and GAPDH cDNA was performed. Finally, a sensitive assay for the relative quantification of circCCT3 using nested real-time quantitative polymerase chain reaction was developed, optimized, and implemented in the patients' samples and cell lines. MM patients exhibited significantly higher intracellular circCCT3 expression in their CD138+ plasma cells, compared to those from SMM patients. In addition, MM patients overexpressing circCCT3 had longer progression-free and overall survival intervals. The favorable prognostic significance of high circCCT3 expression in MM was independent of disease stage (either International Staging System [ISS] or revised ISS [R-ISS]) and age of MM patients. Interestingly, circCCT3 expression could serve as a surrogate molecular biomarker of prognosis in MM patients, especially those of R-ISS stage II. In conclusion, our study sheds new light on the significance of circCCT3 as a promising molecular marker for predicting MM patients' prognosis.

Predicting circRNA-drug resistance associations based on a multimodal graph representation learning framework.

Circular RNA (circRNA) is a class of noncoding RNA that is highly conserved and exhibit exceptional stability. Due to its function as a microRNA sponge, circRNA has gained significant attention as an essential biomarker and potential drug target in the pathogenesis of several cancers. Although many circRNAs have been identified to play a role in cancer resistance, traditional methods are time-consuming and expensive. In this context, computational methods offer a promising way to facilitate the discovery process. However, most existing prediction models focus on the association between circRNAs and drug resistance, without considering the corresponding disease-related information in the circRNA-drug resistance association. Incorporating disease-related information into the prediction of circRNA-drug resistance associations could potentially improve the efficiency and speed of discovering and developing circRNA-targeting drugs. We propose a computational framework, named GraphCDD, for predicting the association between circRNA and drug resistance. Our model utilizes data from three sources, namely circRNA, disease, and drug, to construct three similarity networks that represent the features of circRNA, disease, and drug, respectively. We utilize a multimodal graph neural network to acquire efficient representations of circRNAs, diseases, and drugs by integrating various types of information, and establish a predictive model. The experimental results have validated the effectiveness of our model and provided a promising method in predicting potential associations between circRNA and drug resistance. The source code and dataset of GraphCDD can be found at https://github.com/Ziqiang-Liu/GraphCDD.

Current concepts of the crosstalk between lncRNA and E2F1: shedding light on the cancer therapy.

Long noncoding RNAs (lncRNAs) constitute a distinctive subset of RNA molecules with limited protein-coding potential, which exert crucial impacts on various biological activities. In the context of cancer, dysregulated lncRNAs function as essential regulators that affect tumor initiation and malignant progression. These lncRNAs serve as competitive endogenous RNAs (ceRNAs) through sponging microRNAs and regulating the expression of targeted genes. Moreover, they also directly bind to RNA-binding proteins, which can be integrated into a complex mechanistic network. E2F1, an extensively studied transcription factor, mediates multiple malignant behaviors by regulating cell cycle progression, tumor metastasis, and therapeutic response. Emerging evidence suggests that lncRNAs play a pivotal role in regulating the E2F1 pathway. This review aims to elucidate the intricate gene regulatory programs between lncRNAs and E2F1 in cancer progression. We elaborate on distinct mechanistic networks involved in cancer progression, emphasizing the potential of the lncRNAs/E2F1 axes as promising targets for cancer therapy. Additionally, we provide novel perspectives on current evidence, limitations, and future directions for targeting lncRNAs in human cancers. Fully deciphering the intricate network of lncRNA/E2F1-mediated regulatory mechanisms in cancer could facilitate the translation of current findings into clinical course, such efforts ultimately significantly improve the clinical prognosis of cancer patients.

Actin filament-associated protein 1-antisense RNA1 promotes the development and invasion of tongue squamous cell carcinoma via the AFAP1-AS1/miR-133a-5p/ZIC2 axis.

The present study aimed to explore the biological role and underlying mechanism of the long non-coding RNA actin filament-associated protein 1-antisense RNA1 (lncRNA AFAP1-AS1) in the progression of tongue squamous cell carcinoma (TSCC). A quantitative reverse transcriptase-PCR (RT-qPCR) was conducted to assess relative levels of the miR-133a-5p, lncRNAs AFAP1-AS1 and zinc finger family member 2 (ZIC2) in TSCC cell lines and specimens, whereas ZIC2 protein levels were measured using western blotting. After modifying the levels of expression of lncRNA AFP1-AS1, miR-133a-5p and ZIC2 using lentivirus or plasmid transfection, we examined AKT/epithelial-mesenchymal transition signaling pathway alterations, in vivo carcinogenesis of TSCC in nude mice and in vitro malignant phenotypes. A dual-luciferase reporter assay was conducted to confirm the targeting relationship between ZIC2 and miR-133a-5p, as well as between miR-133a-5p and lncRNA AFAP1-AS1. Based on The Cancer Genome Atlas (TCGA) database, we additionally validated AFP1-AS1. The potential biological pathway for AFP1-AS1 was investigated using gene set enrichment analysis (GSEA). We also evaluated the clinical diagnostic capacities of AFP1-AS1 and clustered the most potential biomarkers with the Mfuzz expression pattern. Finally, we also made relevant drug predictions for AFP1-AS1. In TSCC cell lines and specimens, lncRNA AFAP1-AS1 was upregulated. ZIC2 was upregulated in TSCC cells as a result of lncRNA AFAP1-AS1 overexpression, which also promoted TSCC cell migration, invasion, viability, and proliferation. Via the microRNA sponge effect, it was found that lncRNA AFAP1-AS1 could upregulate ZIC2 by competitively inhibiting miR-133a-5p. Interestingly, knockdown of ZIC2 reversed the biological roles of lncRNA AFAP1-AS1 with respect to inducing malignant phenotypes in TSCC cells. In addition, in vivo overexpression of lncRNA AFAP1-AS1 triggered subcutaneous tumor growth in nude mice implanted with TSCC cells and upregulated ZIC2 in the tumors. The TCGA database findings revealed that AFAP1-AS1 was significantly upregulated in TSCC specimens and had good clinical diagnostic value. The results of GSEA showed that peroxisome proliferator-activated receptor signaling pathway was significantly correlated with low expression of AFP1-AS1. Finally, the results of drug prediction indicated that the group with high AFAP1-AS1 expression was more sensitive to docetaxel, AZD4547, AZD7762 and nilotinib. The upregulation of lncRNA AFAP1-AS1, which increases TSCC cell viability, migration, proliferation and invasion via the AFAP1-AS1/miR-133a-5p/ZIC2 axis, aids in the progression of TSCC.

Integrative Analysis of miRNA and circRNA Expression Profiles and Interaction Network in HSV-1-Infected Primary Corneal Epithelial Cells

Purpose Circular RNAs (circRNAs) are products of alternative splicing with roles as competitive endogenous RNAs or microRNA sponges, regulating gene expression and biological processes. However, the involvement of circRNAs in herpes simplex keratitis remains largely unexplored. Methods This study examines circRNA and miRNA expression profiles in primary human corneal epithelial cells infected with HSV-1, compared to uninfected controls, using microarray analysis. Bioinformatic analysis predicted the potential function of the dysregulated circRNAs and microRNA response elements (MREs) in these circRNAs, forming an interaction network between dysregulated circRNAs and miRNAs. Results A total of 332 circRNAs and 16 miRNAs were upregulated, while 80 circRNAs and six miRNAs were downregulated (fold change ≥2.0 and p < 0.05). Gene ontology (GO) and KEGG pathway analyses were performed on parental genes of dysregulated circRNAs to uncover potential functions in HSV-1 infection. Notably, miR-181b-5p, miR-338-3p, miR-635, and miR-222-3p emerged as pivotal miRNAs interacting with multiple dysregulated circRNAs. Conclusions This comprehensive study offers insights into differentially expressed circRNAs and miRNAs during HSV-1 infection in corneal epithelial cells, shedding light on circRNA-miRNA interactions’ potential role in herpes simplex keratitis pathogenesis.

LncRNA OIP5-AS1 Targets the miR-140-5p/UBR5 Cascade to Promote the Development of Gastric Cancer.

Gastric cancer (GC) is a malignant tumor with the highest incidence among all kinds of malignant tumors in China. Long noncoding RNAs (LncRNAs) have been reported to act as microRNA (miRNAs) sponges and thus play key roles in biological processes and pathogenesis. Thus, this study aimed to investigate the functional effects and the regulatory mechanism of lncRNA opa interacting protein 5-antisense 1 (OIP5-AS1) in gastric cancer cells. The expression of OIP5-AS1, miR-140-5p, Ubiquitin protein ligase E3 component n-recognin 5 (UBR5) was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration, and invasion were assessed using Cell-Counting Kit-8 (CCK-8), Flow cytometry, and Transwell assays. UBR5 protein level was detected by Western blot. Binding between miR-140-5p and OIP5-AS1 or UBR5 was predicted by Starbasev2.0 and TargetScan, and verified using Dual-luciferase reporter assays and RNA pull-down assay. A xenograft mice model was used to evaluate the effects of OIP5-AS1 on tumor growth in vivo. OIP5-AS1 was upregulated in GC cancer and cells. OIP5-AS1 knockdown inhibited cell proliferation, migration, invasion, but induced cell apoptosis in GC. In mechanism, OIP5-AS1 might serve as a sponge for miR-140-5p to enhance UBR5 expression. Moreover, overexpression of miR-140-5p or UBR5 partly reversed the effects of OIP5-AS1 depletion on the progression of GC cells. Furthermore, OIP5-AS1 depletion also suppressed tumor growth in vivo. OIP5-AS1 silencing might suppress proliferation, migration, invasion, and induced apoptosis in GC cells by regulating the miR-140-5p/UBR5 axis.

Macrophages enhance cisplatin resistance in gastric cancer through the transfer of circTEX2.

Cisplatin-based chemotherapy is often used in advanced gastric cancer (GC) treatment, yet resistance to cisplatin may lead to treatment failure. Mechanisms underlying cisplatin resistance remain unclear. Recent evidence highlighted the role of macrophages in cancer chemoresistance. Macrophage-derived exosomes were shown to facilitate intercellular communication. Here, we investigated the cisplatin resistance mechanism based on macrophage-derived exosomes in gastric cancer. Cell growth and apoptosis detection experiments revealed that M2-polarized macrophages increased the resistance of GC cells to cisplatin. qRT-PCR, RNAase R assay, actinomycin D assay and cell nucleo-cytoplasmic separation experiments confirmed the existence of circTEX2 in macrophage cytoplasm, with a higher expression level in M2 macrophages than that in M1 macrophages. Further experiments showed that circTEX2 acted as microRNA sponges for miR-145 and regulated the expression of ATP Binding Cassette Subfamily C Member 1 (ABCC1). Inhibition of the circTEX2/miR-145/ABCC1 axis blocked the cisplatin resistance of gastric cancer induced by M2 macrophages, as evidenced by invitro and invivo experiments. In conclusion, our research suggests that the exosomal transfer of M2 macrophage-derived circTEX2 enhances cisplatin resistance in gastric cancer through miR-145/ABCC1. Additionally, communication between macrophages and cancer cells via exosomes may be a promising therapeutic target for the treatment of cisplatin-resistant gastric cancer.

Circular RNA hsa_circ_0051246 acts as a microRNA-375 sponge to promote the progression of gastric cancer stem cells via YAP1.

Gastric cancer (GC) stem cells play an important role in GC progression. Circular RNAs (circRNAs) act as microRNA (miRNA) sponges and inhibit the biological function of miRNAs in GC cytoplasm. MiRNAs also participate in GC progress. circ_0051246 was shown to be associated with miR-375 after analyzing GC microarray data GSE78091 and GSE83521. The oncoprotein Yes-associated protein 1 (YAP1) is targeted by miR-375 and can be inactivated via the Hippo tumor suppressor pathway. Due to insufficient research on circ_0051246, this study aimed to investigate its relationship with miR-375 and YAP1 in cancer stem cells (CSCs). SGC-7901 CSCs were used to establish knockdown/overexpression models of circ_0051246, miR-375, and YAP1. Malignant phenotypes of CSCs were assessed using Cell Counting Kit 8, colony/sphere formation, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, Transwell, and wound healing assays. To detect the interactions between circ_0051246, miR-375, and YAP1 in CSCs, a dual-luciferase reporter assay and fluorescence in situ hybridization were performed. In addition, 24 BALB/c nude mice were used to establish orthotopic xenograft tumor models. Four groups of mice were injected with CSCs (1 × 106 cells/100 µL) with circ_0051246 knockdown, miR-375 overexpression, or their respective control cells, and tumor progression and gene expression were observed by hematoxylin-eosin staining, immunohistochemistry. Western blot and quantitative real-time PCR were utilized to examine protein and gene expression, respectively. Circ_0051246 silencing reduced viability, promoted apoptosis, and inhibited proliferation, migration and invasion of CSCs. The functional effects of miR-375 mimics were comparable to those of circ_0051246 knockdown; however, the opposite was observed after miR-375 inhibitors treatment of CSCs. Furthermore, circ_0051246-overexpression antagonized the miR-375 mimics' effects on CSCs. Additionally, YAP1 overexpression promoted CSC features, such as self-renewal, migration, and invasion, inhibited apoptosis and E-cadherin levels, and upregulated the expression of N-cadherin, vimentin, YAP1, neurogenic locus notch homolog protein 1, and jagged canonical notch ligand 1. Conversely, YAP1-silenced produced the opposite effect. Moreover, miR-375 treatment antagonized the malignant effects of YAP1 overexpression in CSCs. Importantly, circ_0051246 knockdown and miR-375 activation suppressed CSC tumorigenicity in vivo. This study highlights the promotion of circ_0051246-miR-375-YAP1 axis activation in GC progression and provides a scientific basis for research on the molecular mechanism of CSCs.

Unveiling the LncRNA-miRNA-mRNA Regulatory Network in Arsenic-Induced Nerve Injury in Rats through High-Throughput Sequencing.

Arsenic is a natural toxin which is widely distributed in the environment, incurring diverse toxicities and health problems. Previous studies have shown that long non-coding RNAs (LncRNAs) are also reported to contribute to As-induced adverse effects. LncRNAs are involved in the development of nerve injury, generally acting as sponges for microRNAs (miRNAs). This study aimed to investigate the competitive endogenous RNA (ceRNA) regulatory networks associated with arsenic-induced nerve damage. A total of 40 male Wistar rats were exposed to different doses of arsenic for 12 weeks, and samples were collected for pathological observation and high-throughput sequencing. The ceRNA network was constructed using Cytoscape, and key genes were identified through the PPI network and CytoHubba methods. A real-time quantitative PCR assay was performed to validate gene expression levels. The results showed that subchronic exposure to arsenic in drinking water resulted in pathological and ultrastructural damage to the hippocampal tissue, including changes in neuron morphology, mitochondria, and synapses. Exposure to arsenic results in the dysregulation of LncRNA and mRNA expression in the hippocampal tissues of rats. These molecules participated in multiple ceRNA axes and formed a network of ceRNAs associated with nerve injury. This study also verified key molecules within the ceRNA network and provided preliminary evidence implicating the ENRNOT-00000022622-miR-206-3p-Bdnf axis in the mechanism of neural damage induced by arsenic in rats. These findings provide novel insights into the underlying mechanism of nervous system damage induced by arsenic exposure.

A microRNA sponge, LINC02193, promotes neutrophil activation by upregulating ICAM1 and is correlated with ANCA-associated vasculitis.

To investigate the pathogenic role and underlying mechanisms of long noncoding RNAs (lncRNAs) in ANCA-associated vasculitis (AAV). RNA-sequencing (RNA-seq) was applied to screen the expression profile of lncRNAs in peripheral leukocytes from five AAV patients and five healthy controls (HC). Candidate lncRNAs were preliminarily verified in peripheral leukocytes from 46 AAV patients and 35 HC by qRT-PCR. Then, the identified LINC02193 was further validated in peripheral neutrophils from 67 AAV patients, 45 HC and 64 disease controls. Correlation between LINC02193 levels and disease activity was analysed. Then, a loss-of-function study was conducted to investigate the role of LINC02193 in neutrophils activation. Furthermore, bioinformatics analysis, dual luciferase reporter and RNA immunoprecipitation assays were performed to explore the mechanism of LINC02193 regulating neutrophils activation. A total of 467 upregulated and 412 downregulated lncRNAs were identified in AAV patients. From the top five upregulated lncRNAs, an elevation of LINC02193 was validated in a larger sample of AAV patients, and positively correlated with disease activity. Knockdown of LINC02193 inhibited reactive oxygen species and nitric oxide production, neutrophil extracellular traps release and adhesion to endothelial cells of differentiated human promyelocytic leukaemia HL-60 cells, whereas overexpression of ICAM1 counteracted these effects. Mechanistic analysis demonstrated that LINC02193 acted as an miR-485-5p sponge to relieve the repressive effect of miR-485-5p on ICAM1, thus promoting ICAM1 expression. LINC02193, a novel lncRNA identified in AAV, could function as competing endogenous RNAs for miR-485-5p to promote ICAM1 expression and neutrophils activation, suggesting its potential as a therapeutic target of AAV.

Prediction of circRNA-MiRNA Association Using Singular Value Decomposition and Graph Neural Networks.

A large number of experimental studies have shown that circRNAs can act as molecular sponges of microRNAs, interacting with miRNAs to regulate gene expression levels, thereby affecting the development of human diseases. Exploring the potential associations between circRNAs and miRNAs can help understand complex disease mechanisms. Considering that biological experiments are time-consuming and labor-intensive, this study proposes a computational model using a graph neural network and singular value decomposition (CMASG) for circRNA-miRNA association prediction. Specifically, graph neural networks are used to learn nonlinear feature representations of nodes, followed by matrix factorization algorithms to learn linear feature representations of nodes, and then combined feature representations learned from different perspectives. Finally, the lightGBM algorithm was used for circRNA-miRNA association prediction. The proposed CMASG model achieved an AUC value of 0.8804. The experimental results demonstrate the superiority and effectiveness of the CMASG model in predicting circRNA-miRNA association tasks.

Hippocampal circAnk3 Deficiency Causes Anxiety-like Behaviors and Social Deficits by Regulating the miR-7080-3p/IQGAP1 Pathway in Mice

BackgroundCircular RNAs are highly enriched in the synapses of the mammalian brain and play important roles in neurological function by acting as molecular sponges of microRNAs. circAnk3 is derived from the 11th intron of the ankyrin-3 gene, Ank3, a strong genetic risk factor for neuropsychiatric disorders; however, the function of circAnk3 remains elusive. In this study, we investigated the function of circAnk3 and its downstream regulatory network for target genes in the hippocampus of mice. MethodsThe DNA sequence from which circAnk3 is generated was modified using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9) technology, and neurobehavioral tests (anxiety and depression-like behaviors, social behaviors) were performed in circAnk3+/− mice. A series of molecular and biochemical assays were used to investigate the function of circAnk3 as a microRNA sponge and its downstream regulatory network for target genes. ResultscircAnk3+/− mice exhibited both anxiety-like behaviors and social deficits. circAnk3 was predominantly located in the cytoplasm of neuronal cells and functioned as a miR-7080-3p sponge to regulate the expression of Iqgap1. Inhibition of miR-7080-3p or restoration of Iqgap1 in the hippocampus ameliorated the behavioral deficits of circAnk3+/− mice. Furthermore, circAnk3 deficiency decreased the expression of the NMDA receptor subunit GluN2a and impaired the structural plasticity of dendritic synapses in the hippocampus. ConclusionsOur results reveal an important role of the circAnk3/miR-7080-3p/IQGAP1 axis in maintaining the structural plasticity of hippocampal synapses. circAnk3 might offer new insights into the involvement of circular RNAs in neuropsychiatric disorders.

Regulatory mechanism of circular RNAs in neurodegenerative diseases.

Neurodegenerative disease is a collective term for a category of diseases that are caused by neuronal dysfunction, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Circular RNAs (circRNAs) are a class of non-coding RNAs without the 3' cap and 5' poly(A) and are linked by covalent bonds. CircRNAs are highly expressed in brain neurons and can regulate the pathological process of neurodegenerative diseases by affecting the levels of various deposition proteins. This review is aiming to suggest that the majority of circRNAs influence neurodegenerative pathologies mainly by affecting the abnormal deposition of proteins in neurodegenerative diseases. We systematically summarized the pathological features of neurodegenerative diseases and the regulatory mechanisms of circRNAs in various types of neurodegenerative diseases. Neurodegenerative disease main features include intercellular ubiquitin-proteasome system abnormalities, changes in cytoskeletal proteins, and the continuous deposition of insoluble protein fragments and inclusion bodies in the cytoplasm or nucleus, resulting in impairment of the normal physiological processes of the neuronal system. CircRNAs have multiple mechanisms, such as acting as microRNA sponges, binding to proteins, and regulating transcription. CircRNAs, which are highly stable molecules, are expected to be potential biomarkers for the pathological detection of neurodegenerative diseases such as AD and PD. In this review, we describe the regulatory roles and mechanisms of circRNAs in neurodegenerative diseases and aim to employ circRNAs as biomarkers for the diagnosis and treatment of neurodegenerative diseases.

Circ-ILF2 in oral squamous cell carcinoma promotes cisplatin resistance and induces M2 polarization of macrophages.

Cisplatin (CDDP) chemoresistance is one of the predominant factors in oral squamous cell carcinoma (OSCC) treatment failure. Uncovering the mechanisms underlying CDDP resistance is of great importance in OSCC therapy. Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs, which are reported to participate in the progression of various diseases, including cancer. However, the function of circRNAs in CDDP resistance in OSCC remains unclear. Quantitative reverse transcription PCR was used to search for different circRNAs between OSCC cell lines and CDDP-resistant cell lines. The results showed that circ-ILF2 expression was higher in CDDP-resistant OSCC cell lines. The stability of circ-ILF2 was also confirmed using RNase R and actinomycin D assays. Functional experiments, including cytotoxicity, apoptosis and growth rate assays, showed that upregulation of circ-ILF2 contributes to CDDP resistance. Luciferase reporter-gene, RNA pull-down and quantitative real-time PCR (RT-qPCR) assays showed that circ-ILF2 functions as a microRNA sponge for miR-1252. Luciferase reporter assays, RNA pull-down, RT-qPCR and Western blotting showed that miR-1252 directly targeted and regulated the expression of KLF8. Circ-ILF2 plays an important role in CDDP resistance in OSCC. Circ-ILF2 exerts its function through the miR-1252/KLF8 pathway. In addition, tumour-associated macrophages (TAM) play important roles in cancer progressions, our results showed that circ-ILF2 in OSCC cells induced the M2 polarization of macrophages which provided new thoughts on immunotherapy. Our results suggest that circ-ILF2 may represent a potential therapeutic target in CDDP-resistant OSCC.

Differentially expressed circRNAs in peripheral blood samples as potential biomarkers and therapeutic targets for acute angle-closure glaucoma

Glaucoma is the leading cause of irreversible blindness globally. Circular RNAs (circRNAs) play vital roles in various biological processes as microRNA (miRNA) sponges and, thus, have been investigated as potential biomarkers and therapeutic targets in numerous human diseases. However, the underlying mechanisms of circRNAs in the pathogenesis of glaucoma remain unclear. Therefore, transcriptome sequencing was performed to identify relevant circRNAs in peripheral blood samples from patients with primary angle-closure glaucoma. Bioinformatics analysis was performed to investigate the potential roles of differentially expressed circRNAs (DEcircRNAs) in the pathogenesis of glaucoma. In total, 481 differentially expressed genes in addition to 345 DEcircRNAs were identified in patients with glaucoma. Based on a public database, targeted gene analysis identified 11 DEcircRNAs that potentially regulate the expression of five genes as miRNA sponges in glaucoma. In addition, quantitative reverse transcription PCR analysis verified that expression of the circRNA hsa-circ-0000745 was positively correlated with the expression of NEAT1 as a potential target gene. These results suggest that DEcircRNAs are involved in a gene expression regulatory network related to immune cell function and progression of glaucoma. Thus, DEcircRNAs in peripheral blood are potential biomarkers and therapeutic targets for glaucoma.

N6 -methyladenosine-modified circSTX6 promotes hepatocellular carcinoma progression by regulating the HNRNPD/ATF3 axis and encoding a 144 amino acid polypeptide.

Circular RNAs (circRNAs) play a significant role in the initiation and progression of various cancers, including hepatocellular carcinoma (HCC). Circular syntaxin 6 (circSTX6, also known as hsa_circ_0007905) has been identified as a microRNA (miRNA) sponge in pancreatic adenocarcinoma. However, its full range of functions in terms of protein scaffold and translation remain largely unexplored in the context of HCC. The expression of circSTX6 and its encoded protein was examined in HCC tumour tissues. N6 -methyladenosine (m6 A) on circSTX6 was verified and quantified by methylated RNA immunoprecipitation (Me-RIP), RIP and dual luciferase reporter assays. The biological functions of circSTX6 and its encoded protein in HCC were clarified by in vitro and in vivo experiments. Mechanistically, the interaction between circSTX6 and heterogeneous nuclear ribonucleoprotein D (HNRNPD) was investigated by RNA pull-down, RIP and fluorescence in situ hybridization (FISH)/IF. The regulatory effects of circSTX6 and HNRNPD on activating transcription factor 3 (ATF3) mRNA were determined by mRNA stability and RIP assays. Furthermore, the presence of circSTX6-encoded protein was verified by mass spectrometry. CircSTX6 and its encoded 144 amino acid polypeptide, circSTX6-144aa, were highly expressed in HCC tumour tissues and served as independent risk factors for overall survival in HCC patients. The expression of circSTX6 was regulated by METTL14 in an m6 A-dependent manner. Functionally, circSTX6 accelerated HCC proliferation and tumourigenicity and reinforced tumour metastasis in vitro and in vivo. Mechanistically, circSTX6 acted as a sponge for HNRNPD protein, facilitating its binding to ATF3 mRNA, consequently promoting ATF3 mRNA decay. Meanwhile, circSTX6-144aa promoted HCC proliferation, migration and invasion independent of circSTX6 itself. Collectively, our study reveals that m6 A-modified circSTX6 drives malignancy in HCC through the HNRNPD/ATF3 axis, while its encoded circSTX6-144aa contributes to HCC progression independent of circSTX6. CirSTX6 and its encoded protein hold promise as potential biomarkers and therapeutic targets in HCC.

The Glioblastoma CircularRNAome.

Glioblastoma remains one of the most aggressive cancers of the brain, warranting new methods for early diagnosis and more efficient treatment options. Circular RNAs (circRNAs) are rather new entities with increased stability compared to their linear counterparts that interact with proteins and act as microRNA sponges, among other functions. Herein, we provide a critical overview of the recently described glioblastoma-related circRNAs in the literature, focusing on their roles on glioblastoma cancer cell proliferation, survival, migration, invasion and metastasis, metabolic reprogramming, and therapeutic resistance. The main roles of circRNAs in regulating cancer processes are due to their regulatory roles in essential oncogenic pathways, including MAPK, PI3K/AKT/mTOR, and Wnt, which are influenced by various circRNAs. The present work pictures the wide implication of circRNAs in glioblastoma, thus highlighting their potential as future biomarkers and therapeutic targets/agents.

Novel Insights into Circular RNAs in Metastasis in Breast Cancer: An Update.

Circular RNAs (circRNAs) are single-stranded closed non-coding RNA molecules that are aberrantly expressed and produce tumor-specific gene signatures in human cancers. They exert biological functions by acting as transcriptional regulators, microRNA sponges, and protein scaffolds, regulating the formation of protein-RNA complexes and, ultimately, regulating gene expression. Triple-negative breast cancer (TNBC) is one of the most aggressive cancers of the mammary gland and has a poor prognosis. Studies of circRNAs in TNBC are limited but have demonstrated these molecules' pivotal roles in cell proliferation, invasion, metastasis, and resistance to chemo/radiotherapy, suggesting that they could be potential prognostic biomarkers and novel therapeutic targets. Here, we reviewed the status of actual knowledge about circRNA biogenesis and functions and summarized novel findings regarding their roles in TNBC development and progression. In addition, we discussed recent data about the importance of exosomes in the transport and export of circRNAs in TNBC. Deep knowledge of circRNA functions in metastasis and therapy responses could be an invaluable guide in the identification of novel therapeutic targets for advancing the treatment of TNBC.

Vesicular Release and Uptake of Circular LSD1-RNAs from Non-Cancer and Cancer Lung Cells.

Lysine-specific demethylase 1 (LSD1) is highly expressed in many cancer types and strongly associated with cancer progression and metastasis. Circular RNAs (circRNAs) are produced by back-splicing and influence the interactive RNA network by microRNA and protein sponging. In the present study, we aimedto identify circRNAs that derive from the LSD1-encoding KDM1A gene, and to investigate their potential to be released and uptaken by lung cancer versus non-cancer epithelial cells. We identified four circLSD1-RNAs by RT-PCR with divergent primers, followed by sequencing. The expression level of circLSD1-RNAs was then studied by quantitative PCR on cellular and extracellular fractions of lung cancer (PC9) and non-cancer primary small airway epithelial (PSAE) cells. Moreover, we established the transgenic overexpression of circLSD1-RNAs. We show that circLSD1-RNAs are primarily located in the cytoplasm, but are packaged and released from lung cancer and non-cancer cells by extracellular vesicles (EVs) and ribonucleoprotein (RNP) complexes, respectively. Proteomics demonstrated a different protein pattern of EV fractions released from PC9 versus PSAE cells. Importantly, released circLSD1-RNAs were differently taken up by PSAE and PC9 cells. In conclusion, our findings provide primary evidence that circLSD1-RNAs participate in the intercellular communication of lung cancer cells with the tumor environment.

O37 HLA-L pseudogene as a potential microRNA sponge for regulation of HLA-B

O37 HLA-L pseudogene as a potential microRNA sponge for regulation of HLA-B