Search Results (147)

Postpartum metritis in dairy cows compromises reproductive performance and leads to substantial economic losses. This study investigated the molecular mechanisms underlying metritis by integrating high-throughput circulating microRNA (miRNA) profiling with systems-level bioinformatics. Previously, 30 differentially expressed miRNAs, 16 upregulated and 14 downregulated, were identified in metritis-affected cows compared to healthy controls. Building on these findings, this study predicted miRNA target genes and constructed regulatory networks involving miRNAs, mRNAs, circRNAs, lncRNAs, and snRNAs, alongside protein–protein interaction networks. Functional annotation and KEGG pathway analysis revealed that upregulated miRNAs influenced genes involved in immune activation, apoptosis, and metabolism, while downregulated miRNAs were associated with angiogenesis, immune suppression, and tissue repair. Hub genes such as AKT3, VEGFA, and HIF1A were central to immune and angiogenic signaling, whereas UBE3A and ZEB1 were linked to immune inhibition. Interferon-stimulated genes (e.g., ISG15, RSAD2, CXCL chemokines) were shown to regulate solute carriers, contributing to immune dysregulation. Key pathways included PI3K-Akt, NF-κB, JAK-STAT, insulin resistance, and T cell receptor signaling. Noncoding RNAs such as NEAT1, KCNQ1OT1, and XIST, along with miRNAs like bta-miR-15b and bta-miR-148a, emerged as pro-inflammatory regulators, while bta-miR-199a-3p appeared to exert immunosuppressive effects. These findings offer new insights into the complex regulatory networks driving metritis and suggest potential targets for improving fertility in dairy cows. Full article

Investigations of endogenous plant circular RNAs (circRNAs) in several plant species have revealed changes in their circular RNA profiles in response to biotic and abiotic stresses. Recently, circRNAs have emerged as critical regulators of gene expression. The destructive impacts on agriculture due to plant viral infections necessitate better discernment of the involvement of plant circRNAs during viral infection. However, few such studies have been conducted hitherto. Sobemoviruses cause great economic impacts on important crops such as rice, turnip, alfalfa, and wheat. Our current study investigates the dynamics of plant circRNA profiles in the host Arabidopsis thaliana (A. thaliana) during infections with the sobemoviruses Turnip rosette virus (TRoV) and Rice yellow mottle virus (RYMV), as well as the small circular satellite RNA of the Lucerne transient streak virus (scLTSV), focusing on circRNA dysregulation in the host plants and its potential implications in triggering plant cellular defense responses. Towards this, two rounds of deep sequencing were conducted on the RNA samples obtained from infected and uninfected plants followed by the analysis of circular RNA profiles using RNA-seq and extensive bioinformatic analyses. We identified 760 circRNAs, predominantly encoded in exonic regions and enriched in the chloroplast chromosome, suggesting them as key sites for circRNA generation during viral stress. Gene ontology (GO) analysis indicated that these circRNAs are mostly associated with plant development and protein binding, potentially influencing the expression of their host genes. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed photosynthesis as the most affected pathway. Interestingly, the non-coding exogenous scLTSV specifically induced several circRNAs, some of which contain open reading frames (ORFs) capable of encoding proteins. Our biochemical assays demonstrated that transgenic expression of scLTSV in A. thaliana enhanced resistance to TRoV, suggesting a novel strategy for improving plant viral resistance. Our results highlight the complexity of circRNA dynamics in plant–virus interactions and offer novel insights into potential circRNA-based strategies for enhancing plant disease resistance by modulating the differential expression of circRNAs. Full article

Climate change poses an increasing threat to livestock reproduction, with heat stress (HS) known to significantly impair ovarian function. This study aimed to elucidate the impact of HS on ovarian function and circRNA expression profiles in Hu sheep. Twelve ewes were randomly assigned to a control (Con, n = 6) or HS group (n = 6) and exposed to different temperatures for 68 days. Compared with the Con group, HS significantly increased the respiratory rate (108.33 ± 3.72 vs. 63.58 ± 2.42 breaths/min), pulse rate (121.17 ± 3.98 vs. 78.08 ± 3.31 beats/min), and rectal temperature (40.17 ± 0.14 °C vs. 39.02 ± 0.21 °C; p < 0.05). Concurrently, serum antioxidant levels were markedly decreased, including total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) (p < 0.05). Histological analysis revealed a significant reduction in the numbers of primordial, primary, secondary, and mature follicles, alongside an increase in antral follicles (p < 0.05). TUNEL staining demonstrated enhanced granulosa cell apoptosis (p < 0.05), accompanied by the upregulation of pro-apoptotic genes Bax and Caspase-3 and downregulation of the anti-apoptotic gene Bcl-2, as confirmed by qPCR (p < 0.05). CircRNA sequencing identified 152 differentially expressed circRNAs (120 upregulated, 32 downregulated), and enrichment analyses indicated their involvement in apoptosis, mitophagy, and the FoxO signaling pathway. Collectively, these findings demonstrate that HS impairs ovarian physiology and antioxidant defense, induces follicular damage and cell apoptosis, and alters circRNA expression profiles, providing new insights into the molecular mechanisms underlying HS-induced reproductive dysfunction in Hu sheep. Full article

Objective: Neodymium nitrate (Nd(NO₃)₃) is widely used globally, raising concerns about its occupational and environmental safety. It enters the human body via the digestive system, accumulates in organs, and causes toxicity, including potential hepatotoxicity. However, the role of non-coding RNAs (ncRNAs) in Nd(NO₃)₃-induced liver injury remains unclear. This study aimed to identify key genes and regulatory pathways involved in Nd(NO₃)₃-induced hepatic injury using RNA sequencing (RNA-seq) and differential gene expression analysis. Methods: Mouse hepatocytes (AML12 cells) were exposed to Nd(NO₃)₃, and RNA-seq was performed to analyze the expression profiles of miRNA, lncRNA, circRNA, and mRNA. qPCR was used to validate the RNA-seq results. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the functions and pathways associated with differentially expressed genes (DEGs). Results: Nd(NO₃)₃ exposure altered the expression of ferroptosis-related genes and induced significant changes in mRNA, miRNA, circRNA, and lncRNA expression levels. GO and KEGG analyses revealed that DEGs were closely related to cellular ferroptosis pathways. Specific miRNAs, lncRNAs, and circRNAs were significantly upregulated, suggesting their potential as biomarkers for Nd(NO₃)₃-induced ferroptosis and liver injury. Conclusion: This study provides the first comprehensive transcriptome database for Nd(NO₃)₃-induced liver injury, highlighting the involvement of ncRNAs in hepatotoxicity. These findings offer valuable insights for developing biomarkers and understanding the mechanisms underlying Nd(NO₃)₃-induced hepatic injury. Full article

Background/Objectives: Ovarian follicular cysts (OFCs) in dairy cows represent a significant cause of infertility and share striking similarities with polycystic ovary syndrome (PCOS) in women. This study aimed to elucidate the molecular mechanisms underlying OFCs and their relevance to PCOS by profiling differentially expressed (DE) microRNAs (miRNAs) and constructing integrative RNA interaction networks. Methods: Expression analysis of 84 bovine miRNAs was conducted in antral follicular fluid from normal and cystic follicles using miScript PCR arrays. Bioinformatic tools including miRBase, miRNet, and STRING were employed to predict miRNA targets, construct protein–protein interaction networks, and perform gene ontology and KEGG pathway enrichment. Network analyses integrated miRNAs with coding (mRNAs) and non-coding RNAs (circRNAs, lncRNAs, snRNAs). Results: Seventeen miRNAs were significantly dysregulated in OFCs, including bta-miR-18a, bta-miR-30e-5p, and bta-miR-15b-5p, which were associated with follicular arrest, insulin resistance, and impaired steroidogenesis. Upregulated miRNAs such as bta-miR-132 and bta-miR-145 correlated with inflammation, oxidative stress, and intrafollicular androgen excess. Key regulatory lncRNAs such as Nuclear Enriched Abundant Transcript 1 (NEAT1), Potassium Voltage-Gated Channel Subfamily Q Member 1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1), Taurine-Upregulated 1 (TUG1), and X Inactive Specific Transcript (XIST), as well as circRNA/pseudogene hubs, were identified, targeting pathways involved in metabolism, inflammation, steroidogenesis, cell cycle, and apoptosis. Conclusions: The observed transcriptomic changes mirror core features of human PCOS, supporting the use of bovine OFCs as a comparative model. These findings provide novel insights into the regulatory RNA networks driving ovarian dysfunction and suggest potential biomarkers and therapeutic targets for reproductive disorders. This network-based approach enhances our understanding of the complex transcriptomic landscape associated with follicular pathologies in both cattle and women. Full article

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types due to its late diagnosis, low survival rates, and high frequency of metastasis. Considering the molecular mechanism of PDAC development has not been fully elucidated, this study aimed to shed more light on the molecular regulatory signatures of circular RNAs (circRNAs) in PDAC progression and provide a different perspective to identify potential biomarkers as well as discover candidate repositioned drug molecules for the prevention or treatment of PDAC with network-based integrative analysis. The mRNA, miRNA, and circRNA expression profiles of PDAC were obtained from nine microarray datasets. Differentially expressed genes (DEGs), microRNAs (DEmiRNAs), and circular RNAs (DEcircRNAs) were identified. The competing endogenous RNA (ceRNA; DEG–DEmiRNA–DEcircRNA) regulatory network was constructed, which included 12 DEcircRNAs, 64 DEGs, and 6 miRNAs specific to PDAC. The ADAM12, MET, QKI, SEC23A, and ZEB2 were identified as hub genes and demonstrated significant survival probability for PDAC. In addition to providing novel biomarkers for diagnosis that can be detected non-invasively, the secretion levels of hub genes-associated proteins were found in plasma, serum, and oral epithelium. The drug repositioning analysis revealed vorinostat, meclocycline sulfosalicylate, and trichostatin A, which exhibited significant binding affinities to the hub genes compared to their inhibitors via molecular docking analysis. Full article

The objective of this study is to investigate the molecular regulatory mechanisms of non-coding RNA (ncRNA) during the developmental process of multi-litter sheep ovaries and identify key regulatory genes that enhance the reproductive capacity of sheep. This study selected Small-Tail Han sheep (multi-litter sheep) and Ujumuqin sheep (single-litter sheep) as comparative models, constructed the expression profiles of ncRNAs and mRNAs in ovarian tissues, identified differentially expressed (DE) lncRNAs, circRNAs, miRNAs, and mRNAs, and performed target gene prediction along with functional and signaling pathway enrichment analyses. Reproduction-related pathways were further screened to construct competing endogenous RNA (ceRNA) regulatory networks (lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA). Finally, the dual-luciferase reporter gene assay system was employed to perform the functional validation of the relevant targeted regulatory effects. A comprehensive screening identified 411 DE lncRNAs, 322 DE circRNAs, 26 DE miRNAs, and 29 DEGs from the ovarian tissues of Ujumqin and Small-Tail Han sheep. The results of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that the DE target genes were significantly enriched in pathways associated with cell dedifferentiation, the positive regulation of embryonic development, glycosaminoglycan biosynthesis, Hippo signaling, and other signaling pathways. To identify genes associated with reproductive processes, we performed differential expression screening followed by pathway enrichment analysis, which revealed significant enrichment in reproductive regulatory pathways. Based on these findings, we constructed a ceRNA regulatory network incorporating 22 DEGs, 17 DE lncRNAs, three DE circRNAs, and one DE miRNA. Our analysis revealed that oar-let-7a is involved in signaling pathways such as oocyte meiosis and Hippo, suggesting it may serve as a key miRNA regulating the trait of multiple offspring. The dual-luciferase reporter assay was employed to confirm that oar-let-7a directly targets and regulates the expression of CPEB1. Additionally, it was demonstrated that circRNA803 and lncRNA MSTRG.19726 function as molecular sponges to competitively bind and regulate oar-let-7a. These findings suggest that oar-let-7a mediates the expression of CPEB1 via circRNA803 and lncRNA MSTRG.19726 sponge adsorption, thereby regulating the process of follicular dominance in sheep. The qRT-PCR method was employed to validate the expression patterns of nine randomly selected DEGs, and the results corroborated the reliability of the RNA-seq sequencing data. This study investigated the coordinated regulatory mechanism of DE ncRNAs and their corresponding target genes, identifying a ceRNA network, circRNA803/lncRNA MSTRG.19726-oar-let-7a-CPEB1, which plays a critical role in regulating the process of follicular dominance in sheep. These findings provide fundamental data for uncovering the reproductive potential of sheep and facilitate a comprehensive understanding of their reproductive characteristics, which hold significant guiding implications for enhancing reproductive efficiency. Full article

Rumen acidosis is a widespread digestive disorder in livestock, causing inflammation and lowering animal performance. Unraveling its molecular mechanisms is vital for improving cattle health and welfare. Circular RNAs (circRNAs) are noncoding RNAs functioning as miRNA or protein sponges. This study employed high-throughput RNA sequencing to identify differentially expressed (DE) circRNAs in subacute rumen acidosis (SARA) in Holstein cattle, revealing 65 DE-circRNAs. We constructed a competitive endogenous RNA (ceRNA) network comprising 57 circRNAs, 14 miRNAs, and 22 mRNAs. Key hub nodes included circRNAs (8:69996068-69996853, 16:2614111-2615445, 5:109525933-109531380, 20:63115665-63116774), miRNAs (bta-miR-146b, bta-miR-181a, bta-miR-223, bta-miR-130b), and mRNAs (SLC2A3, SOCS3, DLC1, ARRDC4). Examination of hub circRNA host genes identified 30 DE transcription factors (TFs). Functional and pathway enrichment analysis pinpointed inflammation and immune response pathways, such as NF-kappa B and TNF signaling. This pioneering study offers the first circRNA expression profile and ceRNA network in SARA cattle, indicating circRNAs’ role in inflammation regulation, thus enhancing our understanding of SARA’s systems biology and potential treatment strategies. Full article

Circular RNAs (circRNAs) are increasingly recognized as significant regulators in multiple cancers, such as hepatocellular carcinoma (HCC), frequently affecting microRNA (miRNA) expression. The diagnostic and prognostic roles of circRNAs, specifically circ_0009910 and circ_0027478, in conjunction with miR-1236-3p, in HCC, have not yet been fully investigated. In this pilot study, we assessed the expression levels of circ_0009910, circ_0027478, and miR-1236-3p in plasma samples from 100 patients diagnosed with HCC and 50 healthy controls through reverse transcriptase–quantitative polymerase chain reaction (RT-qPCR). The diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis, and correlations with clinicopathological features were examined. Circ_0009910 and circ_0027478 exhibited significant upregulation in patients with HCC (p < 0.05), whereas miR-1236-3p demonstrated downregulation (p < 0.05). Circ_0009910 demonstrated significant diagnostic accuracy (area under the curve [AUC] = 0.90), effectively differentiating HCC from controls and showing a correlation with tumor size, metastasis, and alpha-fetoprotein (AFP) levels (p < 0.05). Both circ_0009910 and circ_0027478 exhibited a positive correlation with clinicopathological features, whereas miR-1236-3p demonstrated an inverse correlation. Logistic regression validated the diagnostic and prognostic capabilities of these biomarkers. The results indicate that circ_0009910, circ_0027478, and miR-1236-3p, in conjunction with AFP three, present a promising diagnostic and prognostic profile for HCC. Additional validation in larger cohorts is required to establish their clinical utility. Full article

Background: Endometrial receptivity is crucial for successful embryo implantation in assisted reproductive technologies (ARTs). MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) have emerged as important post-transcriptional regulators of endometrial function, although their diagnostic and molecular functions are poorly understood. Methods: A systematic review was conducted following PRISMA 2020 principles and registered in PROSPERO (CRD420251001811). We looked at 28 peer-reviewed publications published between 2010 and 2025 that used endometrial tissue, blood, uterine fluid, saliva, and embryo culture medium to study miRNAs and other non-coding RNAs in endometrial receptivity, recurrent implantation failure (RIF), and infertility. Results: MiRNAs like miR-145, miR-30d, miR-223-3p, and miR-125b influence implantation-related pathways such as HOXA10, LIF-STAT3, PI3K-Akt, and Wnt/β-catenin. Dysregulated expression profiles were linked to inadequate decidualization, immunological imbalance, and poor angiogenesis. CeRNA networks that include lncRNAs (e.g., H19 and NEAT1) and circRNAs (e.g., circ_0038383) further regulate miRNA activity. Non-invasive biomarkers derived from plasma, uterine fluid, and embryo media showed high prediction accuracy for implantation outcomes. Conclusions: MiRNA signatures offer a functional and diagnostic blueprint for endometrial receptivity. This systematic review provides a timely and thorough synthesis of the existing literature, with the goal of bridging the gap between molecular discoveries and therapeutic applications. By emphasizing both the mechanistic importance and diagnostic value of certain miRNA signatures, it paves the way for future precision-based techniques in embryo transfer and endometrial assessment in ART. Full article

Analysis of tumoral RNA from bone marrow (BM) biopsy is essential for diagnosing childhood B-cell acute lymphoblastic leukemia (B-ALL), risk stratification, and monitoring, by detecting fusions and gene expression patterns. However, frequent BM biopsies are invasive and traumatic for patients. Small extracellular vesicles (sEVs) circulating in blood contain a variety of biomolecules, including RNA, that may contribute to cancer progression, offering a promising source of non-invasive biomarkers from liquid biopsies. While most EV studies have focused on small RNAs like microRNAs (miRNAs), the role of longer RNA species, including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), remains underexplored despite their demonstrated potential for risk-based patient stratification when starting from BM biopsies. We used immuno-purification to isolate sEVs from peripheral blood at diagnosis in B-ALL patients and cell model-based conditioned culture medium (CCM) with ETV6::RUNX1 and TCF3::PBX1 fusions. Using whole-transcriptome sequencing targeting transcripts over 200 nt and a novel data analysis pipeline, we identified 102 RNA transcripts (67 mRNAs, 16 lncRNAs, 10 circRNAs, 4 pseudogenes, and 5 others) in patient-derived sEVs. These transcripts could serve as biomarkers for two distinct molecular subgroups of B-ALL, each with different risk profiles at diagnosis. This is the first study characterizing the long transcriptome in blood-derived sEVs for childhood B-ALL, highlighting the potential use of circulating RNAs for improved risk-based stratification. Full article

Extracellular vesicles (EVs) are small capsular bodies released by cells, mediating responses in intercellular communication. The role of EVs in Aβ pathology spreading in the Alzheimer’s disease (AD) brain has been evidenced, although whether this occurs due to the co-transportation of Aβ peptides or contribution of other factors, such as EV-associated transcripts, remains uncertain. In vitro studies of miRNA cargo in neuron-derived extracellular vesicles (NDEVs) show that Aβ hyperexpression alters the transcriptomic profile; however, it is not clear to what extent this causes changes at the organ level. By utilizing datasets from published studies, we generated competing endogenous RNA (ceRNA) networks for miRNAs co-expressed in NDEVs and the brain in different stages of pathology, using both an APP overexpressing neuronal model (in vitro) and brain cortices from 6- and 9-month-old APP/PSEN1 mice (in vivo). Networks integrating information from mRNAs, lncRNAs, and circRNAs showed two candidate lncRNAs (Kcnq1ot1 and Gm42969) and a circRNA (Pum1), while enrichment analyses detected that NDEVs miRNAs signal to other CNS cells and that this signal can be disrupted by Aβ pathology, contributing to the loss of long-term potentiation seen in early AD. Full article

The development and selection of ovarian follicles are essential for continuous egg production in chickens. Non-coding RNAs, particularly circular RNAs (circRNAs), play a critical regulatory role in follicle selection, a process heavily involving granulosa cells (GCs). In this study, we analyzed circRNA expression profiles in small yellow follicles (SYFs) and large yellow follicles (LYFs) of Taihang chickens using RNA sequencing. We identified 14,586 circRNAs, with 57 showing differential expression (DE-circRNAs) between SYFs and LYFs. Functional enrichment analysis revealed that these DE-circRNAs are involved in key biological processes, including signal transduction, cell membrane formation, and nuclear enzymatic regulation. We focused on circGRB14, a circRNA derived from the growth factor receptor-bound protein 14 (GRB14) gene, as a potential regulator of follicle selection. Using qPCR, CCK-8 proliferation assays, and Annexin V/PI apoptosis analysis, we demonstrated that circGRB14 inhibits GC proliferation and promotes apoptosis. In contrast, miR-12264-3p and miR-6660-3p, validated as direct targets of circGRB14 via Dual-Luciferase Reporter assays, exhibited opposing effects by promoting GC proliferation and inhibiting apoptosis. These findings highlight the circGRB14-miR-12264-3p/miR-6660-3p axis as a key regulatory mechanism in GC dynamics during follicle selection. This study provides novel insights into the functional interplay between circRNAs and miRNAs in avian follicle development, offering potential targets for improving egg production in poultry. Full article

We are on the brink of a paradigm shift in both theoretical and clinical oncology. Genomic and transcriptomic profiling, alongside personalized approaches that account for individual patient variability, are increasingly shaping discourse. Discussions on the future of personalized cancer medicine are mainly dominated by the potential of non-coding RNAs (ncRNAs), which play a prominent role in cancer progression and metastasis formation by regulating the expression of oncogenic or tumor suppressor proteins at transcriptional and post-transcriptional levels; furthermore, their cell-free counterparts might be involved in intercellular communication. Non-coding RNAs are considered to be promising biomarker candidates for early diagnosis of cancer as well as potential therapeutic agents. This review aims to provide clarity amidst the vast body of literature by focusing on diverse species of ncRNAs, exploring the structure, origin, function, and potential clinical applications of miRNAs, siRNAs, lncRNAs, circRNAs, snRNAs, snoRNAs, eRNAs, paRNAs, YRNAs, vtRNAs, and piRNAs. We discuss molecular methods used for their detection or functional studies both in vitro and in vivo. We also address the challenges that must be overcome to enter a new era of cancer diagnosis and therapy that will reshape the future of oncology. Full article

The specific expression profile and function of circular RNA (circRNA) in follicular atresia remain largely unknown. Here, the circRNA expression profiles of granulosa cells derived from healthy follicles (HFs) and antral follicles (AFs) in buffalo were analyzed by RNA-seq, and the mechanism of a differentially expressed circRNA (DEcircRNA) circTEC regulating the granulosa cell function that affects follicular atresia was further explored. RNA-seq results showed that a total of 112 DEcircRNAs were identified. Among them, circTEC was highly expressed in HF, and its circular structure was confirmed by RNase R digestion assay, reversed PCR and Sanger sequencing. Functional experiments demonstrated that circTEC promotes the proliferation and steroid hormone synthesis of buffalo granulosa cells (bGCs), and it also inhibits their apoptosis. In-depth mechanism analysis showed that the expression level of circTEC in bGCs from AFs was adversely related to miR-144-5p and consistent with FZD3. CircTEC acts as an endogenous sponge of miR-144-5p to regulate the expression of the target gene FZD3 in AFs, which promotes the proliferation of bGCs and inhibits bGCs apoptosis, thereby inhibiting follicular atresia in buffalo. In summary, our study revealed the regulatory role of the circTEC/miR-144-5p/FZD3 axis during follicular atresia in buffalo. These results provided new insights into the biological mechanism underlying follicular atresia. Full article