Search Results (1,021)

Buffaloes are vital livestock in South-East Asia, attributed to their adaptation to hot and humid climates as well as their capacity to produce high-quality milk and meat. However, the texture of buffalo meat is suboptimal and its slow growth rate restricts the development of the buffalo farming industry. Consequently, studies exploring the key biochemical factors associated with buffalo muscle development have become a research focus. CircRNAs are a class of non-coding RNAs which can function as molecular sponges, participate in protein scaffold formation, and encode short peptides. Previous studies have shown that circRNAs are capable of regulating muscle development; however, relatively few reports have addressed their association with buffalo muscle development. In this study, data from Western blotting and RT-qPCR showed that circCOPS8 significantly enhanced the differentiation of buffalo myoblasts while inhibiting their proliferation (p < 0.05). In contrast, in a mouse model of muscular injury, circCOPS8 prevented the repair of injured muscles. Additionally, RIP-qPCR assays confirmed that circCOPS8 could bind to IGF2BP3 (p < 0.05). Furthermore RT-qPCR and transcriptome sequencing results revealed that circCOPS8 inhibited cell growth by upregulating the expression of genes such as ATR (p < 0.05). Our findings suggested that circCOPS8 promoted the differentiation and apoptosis of buffalo myoblasts while inhibiting their proliferation. The inhibition of cell proliferation was primarily mediated by the binding of circCOPS8 to IGF2BP3 and the promotion of ATR gene expression. This study investigated the role and underlying mechanism of circCOPS8 in buffalo myoblasts, which will extend our understanding of non-coding RNA-mediated regulation of buffalo muscle development, with the ultimate goal of improving the meat quality of buffaloes. Full article

Background/Objectives: Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to sustain proliferation, survive under metabolic stress, and develop therapeutic resistance. While oncogenic signaling pathways regulating cancer metabolism have been extensively studied, increasing evidence indicates that non-coding RNAs (ncRNAs) play essential roles in coordinating metabolic adaptation. This review aims to synthesize current knowledge on long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) as important but relatively less characterized regulators of cancer metabolic adaptation and discuss their potential as biomarkers and therapeutic targets. Methods: We analyzed their roles across multiple types of cancer, prioritizing studies that integrate ncRNA profiling with metabolomics and mechanistic investigations, with particular attention to their diagnostic, prognostic, and predictive value. Results: LncRNAs and circRNAs regulate major metabolic pathways, including glycolysis, mitochondrial function, glutaminolysis, lipid metabolism, and redox balance. They act through transcriptional and epigenetic mechanisms, protein scaffolding, peptide encoding, and miRNA sponging, frequently converging on key regulators such as HIF-1α, c-Myc, p53, AMPK, and mTOR. However, many reported associations remain largely correlative, with limited integration of quantitative metabolic flux analyses and insufficient validation in physiologically relevant models. Conclusions: Although lncRNAs and circRNAs constitute an important context-dependent regulatory layer linking oncogenic signaling to metabolic reprogramming, future studies should combine ncRNA perturbation with stable isotope tracing, fluxomics, spatial metabolomics, long-read sequencing, and single-cell approaches to define causal and spatially resolved metabolic functions. Such integrative strategies may improve biomarker development and support ncRNA-informed, metabolism-oriented therapeutic interventions. Full article

Circular RNAs (circRNAs) are a special category of non-coding RNAs. The latter are known for their pivotal regulatory functions over many cellular processes. In biology, circRNAs exert regulatory functions on many physiological events, most likely through the regulation of gene expression. They are also implicated in a variety of health-related issues in medicine. Advances in molecular techniques and bioinformatics are expected to expand our knowledge of circRNAs, better characterizing their nature and functions. Remarkably, parasites elaborate their own repertoire of circRNAs to regulate different biological aspects. Meanwhile, they reshape the host circRNA landscape, allowing manipulation of different events of host–parasite interplay at molecular levels. We herein present an overview of the putative role of circRNAs in major parasitic infections of medical importance. Surprisingly, we underscore limited knowledge in this domain with many gaps and uncertainties. Scrutiny into the role of circRNAs in host–parasite dynamics could lead to the development of reliable diagnostic tools, or the discovery of novel therapeutic targets or vaccine candidates, for many parasitic infections. Full article

The Swine hepatitis E virus (SHEV) ORF3 protein is pivotal in pathogenesis, yet its regulation of host metabolic homeostasis via endogenous RNA networks remains unclear. This study aimed to elucidate how the SHEV ORF3-mediated circRNA-miRNA network modulates riboflavin metabolism and triggers the aberrant activation of the ko05212 pathway, while also evaluating their physical interactions using AlphaFold 3 structural simulations. To achieve this, high-throughput RNA sequencing, KEGG pathway analysis, and AlphaFold 3 structural simulations were employed to elucidate the circRNA-miRNA-mRNA regulatory network and potential physical interactions. Transcriptomics revealed a “dual activation” of Riboflavin metabolism and Pancreatic cancer pathways. Specifically, we identified an “ENPP Isozyme Switch,” where upregulated hsa_circ_0077855 sponges miR-181a-2-3p, relieving repression of the metabolic enzyme ENPP3 and proto-oncogene KRAS. Furthermore, AlphaFold 3 simulations yielded an extremely low interface predicted Template Modeling score (ipTM = 0.08), refuting direct physical binding, and ORF3 was found to suppress the m6A eraser FTO, suggesting host epigenetic instability. Consequently, SHEV ORF3 induces metabolic remodeling through a dual “epigenetic-post-transcriptional” mechanism: disrupting m6A homeostasis via FTO suppression and constructing a pathogenic ceRNA network via the ENPP3/miR-181a/KRAS axis. These findings highlight the critical role of non-coding RNAs in driving the virus-induced “pre-pathological state”. Full article

The etiology of pediatric cancers is unique, stemming from developmental dysregulation rather than acquired mutations from carcinogenic exposure. These diseases demonstrate vastly different underlying genetic and epigenetic alterations and unique tissue microenvironments which are only now beginning to be explored. While many pediatric cancers have seen improved overall and event-free survival rates thanks to innovations in diagnosis and treatment, many have seen little to no improvement in patient outcomes. This highlights a critical need for additional research into the underlying genetic and epigenetic alterations in these pathologies. Non-coding RNAs (ncRNAs) are functional RNA molecules known to regulate gene expression at epigenetic, transcriptional, and translational levels and can serve as biomarkers of disease. Here, we examine current knowledge of the roles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in the onset, progression, and therapeutic response of pediatric solid tumors. We discuss the current and future potential and pitfalls of these molecules as therapeutics and biomarkers and highlight critical knowledge gaps where future research might provide insight to improve current therapeutic strategies and improve clinical outcomes. Full article

Colorectal cancer (CRC) is a significant cause of cancer mortality in the world, and its etiology is complicated by genetic and epigenetic changes. As one of the most important tumor progression regulators, Zinc Finger E-box Binding Homeobox 1 (ZEB1) is a transcription factor that has a key role in epithelial–mesenchymal transition (EMT), which is essential in the metastasis, drug resistance, and plasticity of cancer cells in CRC. ZEB1 silences the expression of epithelial markers, including E-cadherin, and it induces the development of mesenchymal properties, such as invasion and metastasis, i.e., tumor aggressiveness. ZEB1 drives epigenetic reprogramming in CRC by coordinating histone deacetylation, histone methylation, and DNA methylation of epithelial tumor suppressor gene promoters and by engaging in reciprocal regulatory interactions with non-coding RNAs, including the miR-200 family. Furthermore, multiple oncogenic signaling cascades, including Wnt/β-catenin, TGF-β, NF-κB, MEK-ERK, JAK/STAT3, and HIF-1α, converge on ZEB1 to amplify its transcriptional and epigenetic activity, positioning ZEB1 as a nodal integrator of extracellular cues and epigenetic reprogramming in CRC metastasis. This review integrates three interconnected regulatory layers, i.e., (1) ZEB1’s direct epigenetic control of target gene expression via histone modification and DNA methylation, (2) post-transcriptional regulation of ZEB1 itself by ncRNAs (miRNAs, circRNAs, and lncRNAs) that create feedback circuits modulating layer 1, and (3) upstream modulation of ZEB1 transcriptional activity by oncogenic signaling pathways (Wnt/β-catenin, TGF-β, NF-κB, MEK-ERK, JAK/STAT3, and HIF-1α) to provide a comprehensive picture of ZEB1 in CRC metastasis and its therapeutic implications. Full article

Diabetic kidney disease (DKD) remains a leading cause of end-stage renal disease worldwide, with current therapies often failing to halt its progression due to an incomplete understanding of intrinsic renal molecular mechanisms. This review highlights the pivotal role of non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—as central regulators in the pathogenesis and progression of DKD. We systematically examine how the diabetic milieu dysregulates specific ncRNA profiles in renal cells, driving core pathological processes such as metabolic dysfunction, inflammation, fibrosis, and podocyte injury. Furthermore, we explore the emerging roles of exosomal ncRNAs in intercellular communication and their potential as non-invasive liquid biopsy biomarkers for early diagnosis and disease monitoring. Finally, we discuss the translational prospects of targeting ncRNAs through innovative therapeutic strategies, such as antisense oligonucleotides and miRNA mimics, while addressing the challenges of tissue-specific delivery and clinical implementation. Understanding ncRNA networks offers a refined, systems-level perspective on DKD and opens new avenues for precision diagnostics and targeted interventions aimed at modifying the disease course. Full article

Circular RNA (circRNA) has emerged as an alternative RNA modality for vaccine development due to its covalently closed structure and enhanced molecular stability compared with linear messenger RNA (mRNA). Following the clinical success of mRNA vaccines, circRNA-based platforms have gained attention in both prophylactic and cancer immunization. Unlike linear mRNA, circRNA relies on cap-independent translation and is commonly produced through in vitro transcription coupled with ribozyme-mediated self-circularization. In prophylactic vaccination, circRNA vaccines have demonstrated sustained antigen availability, robust humoral and cellular immune responses, and flexibility in multivalent designs and targeted delivery strategies that support germinal center reactions and neutralizing antibody generation. In cancer vaccines, circRNA has been applied to tumor-associated antigens, neoantigens, and non-canonical peptides, with a primary focus on inducing potent antigen-specific CD8⁺ T cell immunity and enabling combination immunotherapy approaches. This review summarizes recent applications of circRNA-based vaccines in prophylactic and cancer settings, emphasizing in vitro transcription-compatible self-circularization strategies and discussing how methodological choices in RNA design, translation control, purification, and delivery shape immunological outcomes. Full article

Renal cell carcinoma (RCC) represents the most frequent kidney malignancy and remains a major clinical challenge due to its often silent onset, high metastatic potential, and limited responsiveness to conventional chemotherapy. Increasing evidence indicates that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are key regulators of RCC tumorigenesis, progression, and therapy resistance. Rather than providing a purely descriptive overview, this review focuses on emerging mechanistic paradigms through which ncRNAs actively shape tumor behavior and therapeutic response in RCC. This review summarizes current knowledge on the biological and clinical relevance of ncRNAs in RCC, highlighting their dual roles as oncogenic drivers or tumor suppressors through the modulation of pathways involved in proliferation, apoptosis, angiogenesis, invasion, immune evasion, metabolic reprogramming, and ferroptosis. Particular emphasis is placed on mechanistically defined ncRNA regulatory axes controlling ferroptosis, autophagy, metabolic reprogramming, and immune escape, as well as on ncRNA-mediated intercellular communication via extracellular vesicles, which promotes the dissemination of resistance to targeted therapies. The review also addresses ncRNA-based diagnostic and prognostic applications, including miRNA signatures capable of discriminating RCC subtypes and circulating ncRNAs as minimally invasive biomarkers. Moreover, the manuscript discusses ncRNA-mediated mechanisms of resistance to targeted therapies such as sunitinib, sorafenib, and axitinib, emphasizing regulatory networks involving miRNA targets, lncRNA–miRNA sponging, RNA-binding proteins, extracellular vesicle transfer, and epigenetic modulation. Emerging therapeutic opportunities are also addressed, including strategies aimed at inhibiting oncogenic ncRNAs or restoring tumor-suppressive ncRNAs to enhance drug sensitivity and improve patient stratification. Full article

Colorectal cancer (CRC) continues to represent a substantial worldwide health burden. Accurate risk classification and early detection have a significant impact on prognosis. There is still a significant percentage of patients who are diagnosed at advanced stages, notwithstanding the progress that has been made in screening and treatment. Thus, improved molecular tools that encompass the biological complexity of CRC are needed. High-throughput technologies have expanded the biomarker array for CRC screening, prognosis, and therapeutic prediction. This review summarizes evidence on established and emerging molecular tools from tumor tissue, blood, and stool samples, such as DNA mutations, methylation markers, RNA signatures, circulating tumor DNA (ctDNA), circulating cell-free DNA (cfDNA), extracellular vesicles, and multi-omic composite assays. These provide alternatives to conventional approaches that are relatively less invasive and more sensitive. Prognostic biomarkers—such as RAS, BRAF, HER2 alterations, mismatch repair deficiency, tumor mutational burden, methylation signatures, and non-coding RNAs—provide insight into tumor behavior and recurrence risk. To guide targeted therapies, immunotherapies, and chemotherapy response, predictive biomarkers such as RAS/BRAF mutations, HER2 amplification, MSI-H/dMMR status, POLE/POLD1 mutations, DNA methylation panels, miRNAs, lncRNAs, and liquid biopsy markers are crucial. Emerging technologies such as multi-omics, AI-enhanced biomarker discovery, and novel liquid biopsy components (evDNA, circRNAs) pave the way to precision oncology. These molecular tools have the potential to change how CRC is managed by earlier detection and more precise predictive biomarkers. However, large-scale validation and clinical standardization are still crucial for their extensive utilization. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting the central nervous system and is the most common form of dementia in the elderly. Current diagnostic methods are limited in the early and definitive diagnosis of the disease, necessitating the need for new and more reliable biomarkers. Circular RNAs (circRNAs) are non-coding, single-stranded, and highly stable RNA molecules commonly found in the eukaryotic transcriptome. Recent studies have shown that changes in the expression levels of circRNAs may play a role in AD pathogenesis. Furthermore, these molecules are considered as potential non-invasive biomarkers for early diagnosis of AD. In this study, we comprehensively assessed plasma levels of classical neurodegenerative biomarkers [amyloid-β42/amyloid-β40 (Aβ42/Aβ40) ratio, total Tau (tTau), and phosphorylated Tau (pTau)], as well as glial and inflammatory mediators, TAM receptor family members (Tyro3 and AXL), and the newly identified circular RNA molecule hsa_circ_003077. The findings revealed that the expression levels of TAM receptors were significantly increased, the Aβ42/Aβ40 ratio decreased, and both total Tau and phosphorylated Tau levels were significantly increased in AD patients. In the receiver operating characteristic (ROC) curve analysis performed to determine the diagnostic potential of hsa_circ_003077, the area under the curve (AUC) was 0.90 (95% CI: 0.82–0.97). This high AUC value suggests that hsa_circ_003077 may be a strong and novel biomarker candidate for the non-invasive diagnosis of AD. The data obtained confirmed the diagnostic efficacy of classical AD biomarkers and revealed that hsa_circ_003077 is a promising biomarker for early and accurate detection of the disease. However, in order to assess the transferability of these findings to clinical practice, confirmatory studies with larger sample groups are needed to ensure reproducibility of the results. Full article

Gastric cancer (GC), also known as stomach adenocarcinoma (STAD), remains a highly lethal malignancy due to late diagnosis, limited therapeutic efficacy, and frequent metastasis. Although extensive molecular profiling has been performed, post-transcriptional regulatory mechanisms underlying GC progression are still incompletely characterized. In this study, we applied an integrative multi-omics framework to elucidate the regulatory roles and clinical relevance of circular RNAs (circRNAs) in GC. Transcriptomic data of mRNAs, microRNAs, and circRNAs from eight independent GEO datasets were jointly analyzed, resulting in the identification of 249 differentially expressed genes (DEGs), 8 differentially expressed microRNAs (DEmiRNAs), and 4 differentially expressed circRNAs (DEcircRNAs). These molecules were integrated into a competing endogenous RNA (ceRNA) network, enabling systems-level characterization of GC-associated regulatory interactions. Network topology and survival analyses prioritized 13 hub molecules, including IGF2BP3, COL4A1, MMP14, and TGM2, which showed both central network positions and significant associations with patient survival. To explore therapeutic implications, transcriptomics-guided drug repositioning combined with molecular docking analysis identified five candidate compounds—celastrol, fedratinib, pevonedistat, tozasertib, and withaferin A—predicted to target key network hubs. Overall, this in silico study provides a ceRNA-centered regulatory framework for GC and prioritizes biologically informed biomarkers and repositioned drug candidates with potential applicability across other malignancies to converge precision oncology. Full article

Circular RNAs (circRNAs) have emerged as critical regulators of skeletal muscle development, yet the functions of many muscle-derived circRNAs remain uncharacterized. In this study, we identified a novel circRNA, circAIDA, formed by exons 2 to 6 of the AIDA gene, based on bovine muscle sequencing data. Mechanistically, we demonstrate that circAIDA acts as a molecular sponge for miR-29a, thereby relieving the repression of its downstream targets, AKT3 and CLCN2. Functionally, circAIDA promotes bovine myoblast proliferation while inhibiting apoptosis and differentiation in vitro. Furthermore, experiments in vivo suggested circAIDA could attenuate regeneration of skeletal muscle in mice. In brief, we discovered a novel circAIDA/miR-29a interaction that regulates bovine myogenesis, providing new insights into the molecular networks controlling skeletal muscle development. Full article

Receptive endometrium (RE) is essential for mammalian embryo implantation. The establishment of RE is a complex and precise dynamic process regulated by various cytokines, including non-coding RNAs (miRNAs, lncRNAs, and circRNAs). We identified candidate miR-26b-3p and circRNA3890 from our previous endometrial non-coding RNA sequencing data. CircRNA3890 adsorbs miR-26b-3p and inhibits its activity. Mouse double minute 4 (MDM4) is a target gene of miR-26b-3p, and circRNA3890 up-regulates the expression level of MDM4 by inhibiting the activity of miR-26b-3p in dairy goat endometrial epithelial cells (gEECs) in vitro. circRNA3890/miR-26b-3p/MDM4 could promote the proliferation of gEECs through the p53 signaling pathway. MiR-26b-3p could regulate the expression levels of vascular endothelial growth factor A (VEGFA) and leukemia inhibitory factor (LIF) through MDM4 in gEECs, which contributes to the development of endometrial receptivity. Furthermore, the results showed that miR-26b-3p significantly promoted the development of RE and embryo implantation. These findings demonstrate that circRNA3890 targets and adsorbs miR-26b-3p to relieve MDM4 inhibition and promotes EEC proliferation through the p53 signaling pathway. They reveal the regulatory effect of miR-26b-3p on receptive endometrial development and embryo implantation in vitro and in vivo. Full article

Milk fat composition and content are crucial indicators that influence the taste, flavor and nutritional value of milk, and they are regulated by various non-coding RNAs. To enhance milk quality, it is essential to investigate the regulatory mechanisms underlying milk fat metabolism. This study analyzed significantly up-regulated circ_0009058 and circ_0004021 and significantly down-regulated circ_0011934 and circ_0008056 in bovine mammary epithelial cells (BMECs) with high and low milk fat percentages (MFP). RNase R digestion assays and Sanger sequencing were conducted to confirm their presence and high expression in the mammary tissue of dairy cows. Subcellular localization indicated that these RNA may exhibit regulatory functions through the competing endogenous RNA (ceRNA) network. Consequently, a ceRNA regulatory network was constructed, identifying six hub target genes in the ceRNA network (VAV1, PTPN6, PIK3R1, RHOA, ERBB3, PIK3CG) using the CytoHubba and MCODE plugins in Cytoscape (version 3.9). Quantitative real-time PCR (RT-qPCR) and dual luciferase reporter gene assays validated the existence of the interactive regulatory networks circ_0004021/bta-miR-541/PTPN6, circ_0008056/bta-miR-2309/ERBB3, and bta-miR-10175-3p/RHOA in BMECs. Functional validation of miRNAs within the ceRNA network demonstrated that bta-miR-541 and bta-miR-10175-3p reduced triglyceride and cholesterol levels while inhibiting lipid droplet secretion in BMECs. Conversely, the function of bta-miR-2309 was found to be opposite to that of bta-miR-541 and bta-miR-10175-3p. This study identified several critical candidate ceRNA networks involved in fatty acid metabolism in dairy cows through data analysis and a series of experiments. These functional and mechanistic studies provide a theoretical foundation for improving milk quality. Full article