Search Results (1,852)

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver conditions globally. This study aimed to assess the long non-coding RNAs (lncRNAs) growth arrest-specific 5 (GAS5), miR-29a-3p, and neurogenic locus notch homolog protein 2 (NOTCH2) as biomarkers in patients with NAFLD and find out if they are related to any clinical factors. Subjects and Methods: Thirty-eight age-matched healthy persons and thirty-eight NAFLD patients were enrolled. Patients were split into the following three groups: non-alcoholic steatohepatitis (NASH) (n = 12), patients with NAFLD-related cirrhosis (n = 8), and patients with NAFLD-related simple steatosis (n = 18). Real-time PCR was utilized to examine the expression. Results: The lncRNA GAS5 and NOTCH2 were higher in NAFLD cases in comparison to controls. On the other hand, microRNA-29a-3p was underexpressed in NAFLD cases in comparison to controls. Regarding NAFLD diagnosis, lncRNA GAS5 was the best single marker with a sensitivity of 100% and a specificity of 94.7% at the cutoff values of ≥1.16-fold change. Regarding different stages of the disease, the highest level of lncRNA GAS5 was in cirrhosis. lncRNA GAS5 expression, among other studied parameters, is still a significant predictor of NAFLD (adjusted odds ratio of 162, C.I. = 5.7–4629) (p = 0.003). LncRNA GAS5 has a positive correlation with NOTCH2 and a negative correlation with miR-29a-3p. LncRNA GAS5, NOTCH2, and RNA-29a-3p were significantly different in NAFLD cases compared to controls. Conclusions: lncRNA GAS5 appears to be the most effective single marker for detecting NAFLD. LncRNA GAS5 expression is a significant independent predictor of NAFLD. LncRNA GAS5 can differentiate different NAFLD stages. Full article

The midgut of Antheraea pernyi plays a critical role in antiviral defense. However, its transcriptional complexity remains poorly understood. Here, a full-length (FL) transcriptome atlas of A. pernyi midgut was developed by integrating PacBio Iso-Seq and RNA-seq techniques. The transcriptome sequences included 1850 novel protein-coding genes, 17,736 novel alternative isoforms, 1664 novel long non-coding RNAs (lncRNAs), and 858 transcription factors (TFs). In addition, 2471 alternative splicing (AS) events and 3070 alternative polyadenylation (APA) sites were identified. Moreover, 3426 and 4796 differentially expressed genes (DEGs) and isoforms were identified after ApNPV infection, respectively, besides the differentially expressed lncRNAs (164), TFs (171), and novel isoforms of ApRelish (1) and ApSOCS2 (4). Enrichment analyses showed that KEGG pathways related to metabolism were suppressed, whereas GO terms related to DNA synthesis and replication were induced. Furthermore, the autophagy and apoptosis pathways were significantly enriched among the upregulated genes. Protein–protein interaction network (PPI) analysis revealed the coordinated downregulation of genes involved in mitochondrial ribosomes, V-type and F-type ATPases, and oxidative phosphorylation, indicating the disruption of host energy metabolism and organelle acidification. Moreover, coordinated upregulation of genes associated with cytoplasmic ribosomes was observed, suggesting that the infection by ApNPV interferes with host translational machinery. These results show that ApNPV infection reprograms energy metabolism, biosynthetic processes, and immune response in A. pernyi midgut. Our study provides a foundation for elucidating the mechanisms of A. pernyi–virus interactions, particularly how the viruses affect host defense strategies. Full article

Wharton’s jelly mesenchymal stem cells (WJ-SCs) are a promising source for regenerative medicine due to their multipotency, low immunogenicity, and ethical acceptability. Epigenetic regulation plays a crucial role in modulating their proliferation, differentiation, and therapeutic potential. Key mechanisms, including DNA methylation, histone modifications, and non-coding RNAs (e.g., miRNAs and lncRNAs), influence WJ-SC behavior by dynamically altering gene expression without changing the DNA sequence. DNA methylation often silences genes involved in differentiation, while histone acetylation/methylation can activate or repress lineage-specific pathways. Non-coding RNAs further fine-tune these processes by post-transcriptional regulation. Understanding these mechanisms could optimize WJ-SC-based therapies for tissue repair and immune modulation. This review summarizes current insights into epigenetic regulation in WJ-SCs and its implications for regenerative applications. Full article

Background: Preeclampsia (PE) is a pregnancy-specific disease and hypertensive disorder with a multifactorial pathogenesis involving complex molecular regulatory networks. Recent studies highlight the critical role of non-coding RNAs, particularly miRNAs and lncRNAs, in PE development. This study investigates the molecular interaction between miR-7151-5p and the lncRNA KCNQ1OT1 and their functional contributions to PE pathogenesis. Methods: An integrative approach combining RNAhybrid-based bioinformatics, dual-luciferase reporter assays, qRT-PCR, Transwell migration and invasion assays, and RNA sequencing was employed to characterize the binding between miR-7151-5p and KCNQ1OT1 and assess their influence on trophoblast cell function and gene expression. Results: A bioinformatic analysis predicted a stable binding site between miR-7151-5p and KCNQ1OT1 (minimum free energy: –37.3 kcal/mol). The dual-luciferase reporter assay demonstrated that miR-7151-5p directly targets KCNQ1OT1, leading to suppressed transcriptional activity. In HTR8/SVneo cells, miR-7151-5p overexpression significantly downregulated both KCNQ1OT1 and Notch1 mRNA, whereas its inhibition showed no significant changes, suggesting additional regulatory mechanisms of Notch1 expression. Transwell assays indicated that miR-7151-5p overexpression suppressed trophoblast cell migration and invasion, whereas its inhibition enhanced these cellular behaviors. RNA-seq analysis further revealed that miR-7151-5p overexpression altered key signaling pathways, notably the TGF-β pathway, and significantly modulates PE-associated genes, including PLAC1, ANGPTL6, HIRA, GLA, HSF1, and BAG6. Conclusions: The regulatory effect of miR-7151-5p on KCNQ1OT1, along with its influence on trophoblast cell dynamics via Notch1 and TGF-β signaling pathways, highlights its role in PE pathogenesis and supports its potential as a biomarker in early PE screening. Full article

Background: Neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), are increasingly recognized as conditions arising from multifaceted interactions among genetic predisposition, environmental exposures, and epigenetic modifications. Among epigenetic mechanisms, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs), have gained attention as pivotal regulators of gene expression during neurodevelopment. These RNA species do not encode proteins but modulate gene expression at transcriptional and post-transcriptional levels, thereby influencing neuronal differentiation, synaptogenesis, and plasticity. Objectives: This systematic review critically examines and synthesizes the most recent findings, particularly in the post-COVID transcriptomic research era, regarding the role of ncRNAs in the pathogenesis, diagnosis, and potential treatment of neurodevelopmental disorders. Methods: A comprehensive literature search was conducted to identify studies reporting on the expression profiles, functional implications, and clinical relevance of ncRNAs in neurodevelopmental disorders, across both human and animal models. Results: Here, we highlight that multiple classes of ncRNAs are differentially expressed in individuals with ASD and ADHD. Notably, specific miRNAs and lncRNAs demonstrate potential as diagnostic biomarkers with high sensitivity and specificity. Functional studies further reveal that ncRNAs actively contribute to pathogenic mechanisms by modulating neuronal gene networks. Conclusions: Emerging experimental data indicate that the exogenous administration of certain ncRNAs may reverse molecular and behavioral phenotypes, supporting their therapeutic promise. These findings broaden our understanding of neurodevelopmental regulation and open new avenues for personalized diagnostics and targeted interventions in clinical neuropsychiatry. Full article

Cannabis vaping, particularly involving cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), rapidly delivers highly concentrated cannabinoids to the brain, potentially affecting the hippocampus. This study examined differential expression of long noncoding RNAs (lncRNAs) and mRNAs in the hippocampus after acute exposure to vaporized CBD or THC. Male ICR mice were exposed to vaporized CBD or THC (50 mg, n = 5/group), and hippocampal tissues were collected at 1, 3, and 14 days post-exposure. Total RNA sequencing was conducted on day 1 samples, and selected transcripts were validated using qRT-PCR across multiple time points. CBD led to significant up- or downregulation of L3mbtl1, Wnt7a, and Camk2b at day 1. However, Wnt7a showed gradual recovery at days 3 and 14. In the THC group, Grin2a, Gria3, and Golga2 were significantly upregulated, while Drd1, Drd2, Gnal, and Adcy5 were significantly downregulated at day 1. Time-course analysis showed that Drd2 expression returned to baseline by day 14, whereas Adcy5 remained persistently downregulated through days 3 and 14. In the CBD group, NONMMUT069014.2 was upregulated, while NONMMUT033147.2 and NONMMUT072606.2 were downregulated at day 1; notably, NONMMUT072606.2 showed a transient increase at day 3 before returning to baseline. In the THC group, NONMMUT085523.1 and NONMMUT123548.1 were upregulated, whereas NONMMUT019734.2, NONMMUT057101.2, and NONMMUT004928.2 were downregulated, with most showing gradual recovery by day 14. Correlation analysis revealed that THC-responsive lncRNAs—including NONMMUT004928.2, NONMMUT057101.2, and NONMMUT019734.2—were strongly associated with downregulated mRNAs such as Drd2 and Adcy5. These findings highlight cannabinoid-specific hippocampal transcriptomic responses and suggest potential regulatory roles for lncRNA–mRNA interactions in cannabinoid-induced neural changes. Full article

Asthma, the most common chronic respiratory condition in children, involves airway inflammation, hyper-responsiveness, and frequent exacerbation that worsen the airflow and inflammation. Exosomes, extracellular vesicles carrying microRNAs (miRNAs), play a key role in cell communication alongside other types of communication and are promising markers of asthma severity. This study compares exosomal miRNA and long non-coding RNA (lncRNA) profiles in boys with asthma, focusing on differences between those with normal lung functions and those with severe airflow obstruction. This study enrolled 20 boys aged 9–18 years with asthma, split into two groups based on their lung function. Ten had normal lung function (NLF; FEV1/FVC > 0.84, FEF75% > 69% predicted), while ten had severe airflow obstruction (SAO; FEV1/FVC < 0.70, FEF75 < 50% predicted). Saliva and blood samples were collected. Exosomes were isolated, quantified, and analyzed via small RNA sequencing to identify differentially expressed (DE) miRNA and lncRNA profiles. Bioinformatic tools were then used to explore potential miRNA biomarkers linked to asthma severity. SAO subjects were more likely to exhibit allergen sensitization, higher IgE levels, and more eosinophils. We identified 27 DE miRNAs in plasma and 40 DE miRNAs in saliva. Additionally, five key miRNAs were identified in both saliva and plasma which underline important pathways such as neurotrophins, T-cell receptor, and B-cell receptor signaling. We further outlined key features and functions of miRNAs and long non-coding RNAS (lncRNAs) and their interactions in children with asthma. This study identified DE miRNAs and lncRNAs in children with SAO when compared to those with NLF. Exosomal miRNAs show strong potential as non-invasive biomarkers for personalized asthma diagnosis, treatment, and monitoring. These RNA markers may also aid in tracking disease progression and response to therapy, thereby supporting the need for future studies aimed at applications in precision medicine. Full article

Herpesviruses are DNA viruses that evade the immune response and persist as lifelong infections. Human gamma-herpesviruses Epstein–Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV) are oncogenic; they can lead to cancer. Oncogenic viruses are responsible for 10–15% of human cancer development, which can have poor prognoses. Non-coding RNAs (ncRNAs) are RNAs that regulate gene expression without encoding proteins, and are being studied for their roles in viral immune evasion, infection, and oncogenesis. ncRNAs are classified by their size, and include long non-coding RNAs, microRNAs, and circular RNAs. EBV and KSHV manipulate host ncRNAs, and encode their own ncRNAs, regulating host processes and immune responses. Viral ncRNAs regulate host functions by post-transcriptionally modifying host RNAs, and by serving as mimics of other host RNAs, promoting immune evasion. ncRNAs in gamma-herpesvirus infection are also important for tumorigenesis, as dampening immune responses via ncRNAs can upregulate pro-tumorigenic pathways. Emerging topics such as RNA modifications, target-directed miRNA degradation, competing endogenous RNA networks, and lncRNA/circRNA–miRNA interactions provide new insights into ncRNA functions. This review compares ncRNAs and the mechanisms of viral immune evasion in EBV and KSHV, while also expanding on recent developments in the roles of ncRNAs in immune evasion, viral infection, and oncogenesis. Full article

Background: Long non-coding RNAs (lncRNAs) are increasingly recognized as pivotal regulators in both inflammatory and neoplastic skin disorders. Their implications in numerous biological processes, including gene expression, immune responses, and epidermal homeostasis, suggest potential applications as diagnostic and prognostic markers, as well as therapeutic targets. Methods: We conducted a literature search on lncRNAs involved in both psoriasis and cutaneous squamous cell carcinoma (cSCC), highlighting overlapping pathogenic mechanisms. Results: Several lncRNAs, such as HOTAIR, MALAT-1, H19, and uc.291, display dysregulated expression in both psoriasis and cSCC, influencing keratinocyte proliferation and apoptosis, immune modulation, cytokine signaling, and the synthesis of epidermal proteins. Conclusions: The intersection of lncRNA function in chronic inflammation and skin carcinogenesis underscores their role in mediating the transition from psoriatic inflammation to tumorigenesis, offering new insights into disease susceptibility; further investigation through functional studies and clinical validation are required. The study of lncRNA-mediated molecular pathways is particularly relevant given the increased risk of non-melanoma skin cancers and lymphoproliferative disorders among patients with chronic and severe forms of psoriasis. Full article

Lead (Pb) exposure poses a significant public health concern due to its neurotoxic effects. While mitochondrial dysfunction is implicated in lead neurotoxicity, the precise molecular mechanisms, particularly the role of non-coding RNA-mediated competing endogenous RNA networks, remain underexplored. SH-SY5Y neuroblastoma cells were treated with 10 μM lead acetate. Cell viability was assessed by Cell Counting Kit-8 (CCK-8). Mitochondrial ultrastructure and quantity were analyzed via transmission electron microscopy (TEM). Key mitochondrial dynamics proteins were examined by Western blot. Comprehensive transcriptome sequencing, including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs) and mRNAs, was performed followed by functional enrichment and ceRNA network construction. Selected RNAs and hub genes were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Lead exposure significantly reduced SH-SY5Y cell viability and induced mitochondrial damage (decreased quantity, swelling, fragmentation). Western blot confirmed an imbalance in mitochondrial dynamics, as indicated by decreased mitofusin 2 (MFN2), increased total and phosphorylated dynamin-related protein 1 (DRP1). Transcriptomic analysis revealed widespread differential expression of lncRNAs, circRNAs, miRNAs, and mRNAs. Enrichment analysis highlighted mitochondrial function and oxidative stress pathways. A ceRNA network identified five key hub genes: SLC7A11, FOS, HMOX1, HGF, and NR4A1. All validated RNA and hub gene expression patterns were consistent with sequencing results. Our study demonstrates that lead exposure significantly impairs mitochondrial quantity and morphology in SH-SY5Y cells, likely via disrupted mitochondrial dynamics. We reveal the potential regulatory mechanisms of lead-induced neurotoxicity involving ceRNA networks, identifying hub genes crucial for cellular stress response. This research provides a foundational framework for developing therapeutic strategies against lead-induced neurotoxicity. Full article

Uterine fibroids (leiomyomas) are benign tumors whose growth is influenced by estrogen and progesterone. This study aimed to compare the profiles of differentially expressed long non-coding RNAs (lncRNAs) in fibroids from postmenopausal and premenopausal women to identify hormone-responsive lncRNAs. RNA sequencing was performed on six pairs of fibroid (Fib) and adjacent myometrium (Myo) tissues from postmenopausal women. Out of 7876 normalized lncRNAs, 3684 were differentially expressed (≥1.5-fold), with 1702 upregulated and 1982 downregulated in Fib. Comparative analysis with a previously published premenopausal dataset identified 741 lncRNAs that were altered based on their menopausal status, including 62 lncRNAs that were uniquely dysregulated in postmenopausal samples. Overall, 9 lncRNAs were selected for validation by PCR in an expanded cohort of 31 postmenopausal and 84 premenopausal paired samples. Several lncRNAs, including LINC02433, LINC01449, SNHG12, H19, and HOTTIP, were upregulated in premenopausal Fib but not in postmenopausal ones, while ZEB2-AS1 displayed the opposite pattern. CASC15 and MIAT were elevated in Fib from both groups, although the increase was less pronounced in the postmenopausal group. LINC01117 was significantly downregulated in postmenopausal Fib, with no change observed in premenopausal samples. Additionally, analysis based on MED12 mutation status revealed that lncRNAs such as LINC01449, CASC15, and MIAT showed limited or reduced differential expression (mutation-positive vs. mutation-negative) in postmenopausal patients compared to the premenopausal group. These findings indicate that lncRNA expression in fibroids is modulated by menopausal status, likely reflecting hormonal influence. Hormone-responsive lncRNAs may play key roles in fibroid pathogenesis and represent potential targets for therapeutic intervention. Full article

Pear (Pyrus pyrifolia) is an important deciduous fruit tree that requires a specific period of low-temperature accumulation to trigger spring flowering. The warmer winter caused by global warming has led to insufficient winter chilling, disrupting floral initiation and significantly reducing pear yields in Southern China. In this study, we integrated targeted phytohormone metabolomics, full-length transcriptomics, and proteomics to explore the regulatory mechanisms of dormancy in ‘Mixue’, a pear cultivar with an extremely low chilling requirement. Comparative analyses across the multi-omics datasets revealed 30 differentially abundant phytohormone metabolites (DPMs), 2597 differentially expressed proteins (DEPs), and 7722 differentially expressed genes (DEGs). Integrated proteomic and transcriptomic expression clustering analysis identified five members of the dormancy-associated MADS-box (DAM) gene family among dormancy-specific differentially expressed proteins (DEPs) and differentially expressed genes (DEGs). Phytohormone correlation analysis and cis-regulatory element analysis suggest that DAM genes may mediate dormancy progression by responding to abscisic acid (ABA), gibberellin (GA), and salicylic acid (SA). A dormancy-associated transcriptional regulatory network centered on DAM genes and phytohormone signaling revealed 35 transcription factors (TFs): 19 TFs appear to directly regulate the expression of DAM genes, 18 TFs are transcriptionally regulated by DAM genes, and two TFs exhibit bidirectional regulatory interactions with DAM. Within this regulatory network, we identified a novel pathway involving REVEILLE 6 (RVE6), DAM, and CONSTANS-LIKE 8 (COL8), which might play a critical role in regulating bud dormancy in the ‘Mixue’ low-chilling pear cultivar. Furthermore, lncRNAs ONT.19912.1 and ONT.20662.7 exhibit potential cis-regulatory interactions with DAM1/2/3. This study expands the DAM-mediated transcriptional regulatory network associated with bud dormancy, providing new insights into its molecular regulatory mechanisms in pear and establishing a theoretical framework for future investigations into bud dormancy control. Full article

Kazakh mares have drawn significant attention for their outstanding lactation traits. Lactation, a complex physiological activity, is modulated by multiple factors. This study utilized high-throughput sequencing to conduct whole-transcriptome sequencing analysis on the mammary gland tissue of eight Kazakh mares, of which four were pregnant and four were non-pregnant, to systematically reveal the molecular regulatory mechanisms. The results showed differential expression in 2136 mRNAs, 180 lncRNAs, 104 miRNAs, and 1162 circRNAs. Gene ontology functional annotation indicates that these differentially expressed genes are involved in multiple key biological processes, such as the cellular process (BP), metabolic process, and biological regulation. Kyoto Encyclopedia of Genes and Genomes analysis suggests that the differentially expressed genes are significantly enriched in essential pathways such as cytokine–cytokine receptor interaction, the chemokine signaling pathway, and the PI3K-Akt signaling pathway. Additionally, this study constructed a competing endogenous RNA (ceRNA) regulatory network based on the differentially expressed genes (|log₂FC| > 1, FDR < 0.05), offering a novel perspective for revealing the functional regulation of the mammary gland. This study compared genomic differences in mammary gland tissue of pregnant and non-pregnant Kazakh mares and identified candidate genes that are closely related to lactation regulation. It found that various genes, such as PIK3CG, IL7R, and SOD2, play central regulatory roles in activating mammary gland functions. These findings provide theoretical support for explaining the molecular mechanisms underlying the mammary gland development of Kazakh mares. Full article

Meniscal degradation is considered a driver of osteoarthritis (OA) progression, but the underlying mechanisms leading to age-related meniscus degeneration remain unknown. This study aimed to identify key genes and pathways involved in meniscal degradation through a computational analysis. Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differential expression gene (DEG) analysis was performed using DESeq2 accompanied by functional enrichment analysis, protein–protein interaction (PPI) and clustering analysis. Additionally, gene set enrichment analysis (GSEA) was performed. A total of 85 mRNAs (DEMs) and 8 long non-coding RNAs (DE LncRNAs) were found to be differentially expressed in OA meniscus tissues. Among 85 DEMs, 12 genes were found to be known OA-related genes, whereas 15 genes acted as transcription regulators, including RUNX2 and TBX4, which were identified as effector genes for OA. Enrichment analysis revealed the implication of DEMs in cartilage-degradation-related processes, including inflammatory pathways, lipid metabolism, extracellular matrix organization and superoxide/nitric oxide metabolic processes. Target genes of DE lncRNAs were found to be involved in chondrocyte differentiation and pathways related to cartilage degradation. A comparative analysis of meniscus, synovium and cartilage datasets identified three genes (GJB2, PAQR5 and CLEC12A) as being differentially expressed across all three OA-affected tissues, which were implicated in inflammatory and cholesterol metabolism processes. Our results support that shared mechanisms lead to meniscal and cartilage degradation during OA progression, providing further insights into the processes underlying OA pathogenesis and potential therapeutic targets for knee OA. Full article

The active form of vitamin D₃, 1,25(OH)₂D₃, exerts hierarchical control over gene expression, initially targeting transcription factors (TFs) that drive downstream responses. Here, we profile the transcriptional landscape of primary keratinocytes (HPEKp) and squamous cell carcinoma (SCC) cells in response to 1,25(OH)₂D₃, revealing a distinct shift in regulatory targets. While TFs accounted for 9.23% of differentially expressed genes (DEGs) in keratinocytes, this proportion dropped to 4.9% with prolonged exposure. In contrast, SCC cells displayed a five-fold reduction in TFs deregulation and a concurrent enrichment of long non-coding RNAs (lncRNAs), which comprised 22.25% of DEGs after 24 h treatment, with 81% upregulated. Integrative transcriptomic and in silico analyses showed that lncRNA induction was predominantly VDR-dependent, partially RXRA-dependent, and PDIA3-independent. Notably, 90% of deregulated lncRNAs were atypical for head and neck SCC. Several of these lncRNAs exhibit potential antitumor properties and may modulate SCC cell responsiveness to interferon-gamma (IFN-γ). In conclusion, these findings suggest that in SCC cells, the regulation of lncRNA expression—rather than transcription factor modulation—may represent a mechanism of the cellular response to 1,25(OH)₂D₃. Full article