Search Results (2,980)

Long non-coding RNAs (lncRNAs) are key regulators of gene expression and play critical roles in cancer-related signaling networks. Dysregulation of antagonistic lncRNAs may contribute to hepatocarcinogenesis and disease progression. This study investigated the clinical significance and predictive value of two biologically antagonistic lncRNAs, UFC1 and PTENP1, as circulating biomarkers for hepatocellular carcinoma (HCC) in an Egyptian cohort. Expression levels of these lncRNAs were quantified in 100 HCC patients and 100 age- and sex-matched healthy controls. UFC1 was significantly upregulated (~2.9-fold), while PTENP1 was markedly downregulated (~4-fold) in HCC patients, with a strong inverse correlation (r = −0.609, p < 0.001). Both lncRNAs demonstrated higher diagnostic accuracy compared to alpha-fetoprotein (AFP); combining them with AFP further enhanced overall performance. UFC1 expression was increased progressively with advancing fibrosis grade and Barcelona Clinic Liver Cancer (BCLC) stage, while PTENP1 levels diminished with BCLC stage. Logistic regression confirmed UFC1 as an independent risk factor and PTENP1 as a protective factor for HCC. In conclusion, the blood-based UFC1/PTENP1 panel exhibits promising diagnostic accuracy and is associated with disease severity, surpassing AFP. Their fibrosis-associated dysregulation suggests a role in early hepatocarcinogenesis. This antagonistic lncRNA signature represents a potential, non-invasive tool for HCC detection and risk stratification, meriting further clinical validation. Full article

Bipolar disorder (BD) is characterized by mood swings between mania and depression, sharing overlapping symptomatic and genetic risk factors with other mood disorders. Long non-coding RNAs (lncRNAs) show specific spatiotemporal precision in distinct cell types in the human brain, and understanding the precise mechanisms of lncRNAs in mood switching in BD is fundamental to deciphering the key molecular networks underlying BD diagnosis and therapy. In this review, we summarize the classification of BD subtypes, the differences between BD and multiple mood disorders, and the functional potential of lncRNAs in BD. Future studies of these lncRNAs will facilitate the development of RNA-based diagnosis for BD. Full article

Cancer immunotherapy has transformed the clinical management of several malignancies; however, its efficacy remains limited in tumors with low mutational burden and restricted availability of classical mutation-derived neoantigens. In this context, increasing evidence indicates that the tumor immunopeptidome extends far beyond canonical protein-coding regions, incorporating peptides derived from non-coding transcripts through non-canonical translation mechanisms. Long non-coding RNAs (lncRNAs), traditionally regarded as transcriptional or post-transcriptional regulators, have recently emerged as an unexpected source of small open reading frame-encoded peptides (lncPEPs). A subset of these peptides is processed and presented by major histocompatibility complex class I molecules, generating tumor-specific neoantigens capable of eliciting CD8⁺ T cell responses. Owing to the high tissue and context specificity of lncRNA expression, lncRNA-derived neoantigens offer unique advantages over mutation-based targets, including increased tumor selectivity and potential recurrence across patient subsets. In this review, we synthesize current knowledge on the biogenesis, detection, and immunogenic potential of lncRNA-derived peptides, highlighting experimental and computational strategies for their identification within the cancer immunopeptidome. We discuss the challenges associated with their validation and clinical translation, as well as their relevance for the development of vaccines and adoptive T cell–based therapies. Finally, we illustrate these concepts using epithelial ovarian cancer as a representative model of low-mutational-burden tumors, where lncRNA-derived neoantigens may help overcome current limitations of immunotherapy and enable patient stratification for personalized treatment approaches. Full article

Radiation-responsive promoters represent a functionally distinct class of transcriptional regulatory elements that translate genotoxic stress signals into quantifiable gene expression outputs. These promoters occupy a unique mechanistic position within the broader radiation biomarker landscape: rather than directly measuring molecular damage products, they report the cellular interpretation of radiation-induced stress through coordinated gene regulatory networks. This review provides a systematic analysis of five major classes of radiation-responsive promoters—microRNA (miRNA) promoters, tRNA-derived small RNA (tsRNA) promoters, acute-phase protein gene promoters, DNA repair gene promoters, and long non-coding RNA (lncRNA) promoters—with emphasis on their regulatory logic, dose-response characteristics, and current evidence for clinical deployment. We further describe four complementary screening strategies: homology-based conservation analysis, functional genomics and transcriptomics, epigenetic modification profiling, and synthetic biology promoter engineering. Applications spanning biosensor development, biological dosimetry, treatment response prediction, and radiation-guided gene therapy are evaluated within a two-track framework that distinguishes biomarker-oriented applications (Track A) from tool-oriented reporter gene systems (Track B). Critical appraisal of current limitations—including insufficient clinical-grade validation, absence of standardized dose-response curves, and reproducibility deficits—is integrated throughout. Future priorities include multi-center prospective validation studies, FAIR-compliant data infrastructure, AI-driven multi-omics integration, and point-of-care detection platforms. Radiation-responsive promoter biology holds significant potential for advancing precision radiotherapy and nuclear emergency medical response, contingent upon systematic closure of the current evidence gap relative to established gold-standard cytogenetic methods. Full article

Background: Hypertension is an important target for primordial prevention of complex, noncommunicable diseases, and its prevalence remains high across populations. The urban population in India is at a high risk of hypertension, but the genetic basis of hypertension in this population remains poorly understood. Methods: We conducted a pooled whole-blood genome-wide association study of 28 pools representing 1402 participants of the Diabetes In Sindhi Families In Nagpur (DISFIN) study, which enrolled families of probands with type 2 diabetes (T2D). Genotyping was done using Illumina’s Global Screening Array. Results: From a total of 608,550 single-nucleotide variants, 191 were found to be significantly associated with hypertension even after adjusting for metabolic comorbidities, batch effects, pooling error, kinship status, and pooling variation. These variants mapped to 180 well-characterized genes comprising 55 (31%) genes, and encode long noncoding RNAs (lncRNAs). Many of the genes significantly associated with hypertension (including 35% of the lncRNAs) have also been reported by other studies. However, we identified novel genes (SBF2, ARHGAP12, EPAS1, CLEC16A, and LRPPRC) to be associated with hypertension. The most significantly associated lncRNA gene was FLYWCH-AS1. Bioinformatic analyses indicated that these novel genes are likely to have functional importance in hypertension. Conclusions: Our study thus points to the potential candidate genes associated with hypertension in endogamous Sindhi families with T2D patients. The replicable and functional role of these candidate genes should be investigated in future studies. Full article

Scaevola taccada, as a key dominant plant in coastal ecosystems, plays an irreplaceable role in sand fixation, shoreline protection, and maintaining the ecological stability of coastal zones. To investigate the effects of drought stress on the Binghai plant Scaevola taccada seedlings, a natural drought treatment was applied. Physiological indicators were measured at 0, 10, 25, and 40 days of stress, and 5 days after rewatering. Transcriptome sequencing and long non-coding RNA (lncRNA) analysis were also conducted to reveal the drought response mechanisms and molecular regulatory networks. The results showed that: (1) Prolonged drought significantly inhibited growth, with relative height increase, leaf number, and relative water content declining by 46.8%, 37.2%, and 63.4%, respectively, at T40 compared to the control. (2) In terms of photosynthetic physiology, Rubisco activity, RCA activity, SPAD value, Fv/Fm, and qP all continuously declined with increasing stress, while NPQ increased, suggesting damage to the photosynthetic system but also the activation of energy dissipation mechanisms to alleviate photooxidative stress. (3) The antioxidant system played a crucial role in the drought response. Under drought stress, the activities of SOD, POD, and CAT, and MDA content, underwent significant changes, with antioxidant enzyme activities rebounding notably after rewatering. (4) Transcriptome analysis revealed that differentially expressed mRNAs and lncRNA-targeted genes were significantly enriched in the ‘photosynthesis’ and ‘carbon metabolism’ pathways. Key genes involved, including PSAD-1, PSAL, NPQ4, six LHCs, BAM3, BAM1, SSII-A, and FRK1, were identified as core components of the regulatory network. In summary, Scaevola taccada effectively responds to drought stress through multi-level mechanisms, including photosynthetic regulation, carbon metabolism regulation, antioxidant defense, and transcriptional reprogramming, demonstrating strong drought resistance and post-rewatering recovery potential. These findings provide scientific evidence for plant selection and application in ecological restoration projects in coastal areas in the context of global climate extremes. Full article

Bladder cancer (BCa) is a major global urinary tract malignancy characterized by high incidence, frequent recurrence, and significant mortality. Early diagnosis is crucial for improving prognosis and minimizing invasive procedures; however, current standard techniques, cystoscopy and urine cytology, are limited by invasiveness, cost, low sensitivity, and subjectivity. This has spurred the development of non-invasive diagnostic strategies based on urine analysis. This review highlights five emerging approaches: AI-augmented urine cytology, genomic biomarker assays (e.g., PCR and NGS for mutations and copy-number variations), DNA methylation profiling, RNA biomarkers (mRNA, miRNA, lncRNA), and protein/peptide/metabolite detection utilizing ELISA, SERS, nanozymes, and mass spectrometry. We assess the diagnostic accuracy, innovations, and clinical potential of each, while addressing persisting issues such as lack of standardization, high costs, and insufficient sensitivity for early-stage lesions. Future directions include integrating multi-omics data with AI, advancing point-of-care devices, and conducting large-scale multicenter trials. Together, these developments promise to shift BCa management toward molecular-based early detection, enabling more precise, non-invasive, and personalized patient care. Full article

Cellular therapy using human cardiac mesenchymal progenitor cells (hMPCs) for regenerative medicine is hindered by poor cell survival and senescence. Long non-coding RNAs (lncRNAs) are critical regulators of cellular processes, yet their role in cardiac aging remains underexplored. Here, lncRNA microarray profiling identified a novel lncRNA, XLOC_002543, upregulated in hMPCs preconditioned with cobalt protoporphyrin (CoPP), which was named CoPP-Induced and SFPQ-Associated RNA Transcript (CISAT) due to its interaction with splicing factor proline and glutamine rich (SFPQ), confirmed via RNA pull-down and immunoprecipitation. CISAT was the only highly expressed transcript among seven lnc-ANKMY1-5 variants in hMPCs, as shown by RT-PCR. Notably, CISAT expression decreased in aging/senescent hMPCs, correlating with elevated p16^INK4A, a senescence marker. Overexpression of CISAT reduced p16^INK4A levels; enhanced hMPC survival, proliferation, and migration; and increased antioxidant and anti-apoptotic protein expression, while CISAT knockdown reduced resistance to H₂O₂-induced oxidative stress. In vivo, intramyocardial transplantation of CISAT-overexpressed hMPCs in an immune-deficient murine myocardial infarction model reduced fibrosis, promoted angiogenesis, and preserved cardiac function. Mechanistically, CISAT interacts with SFPQ to regulate NRF2-mediated redox homeostasis and inhibits p38 MAPK phosphorylation, mitigating senescence and enhancing cell survival. These findings suggest that targeting CISAT to modulate redox signaling and p38 MAPK pathways in aging hMPCs could improve their therapeutic efficacy for myocardial repair in heart disease. 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

Background/Objectives: Lung cancer remains a major global health burden, largely driven by cigarette use. Although electronic cigarettes (e-cigarettes) are viewed as safer alternatives due to their reduced chemical load, growing evidence shows their vapor can disrupt cellular transcriptomes, including long noncoding RNAs (lncRNAs). In this study, we examined the regulation and function of vape-associated lncRNA transcript 1 (VALT1), a novel transcript upregulated in the oral transcriptomes of e-cigarette users and similarly elevated in non-small-cell lung cancer (NSCLC) tumors. Methods: Publicly available RNA-seq datasets were analyzed, and VALT1 was identified as an e-cigarette-responsive lncRNA. Its dose-dependent induction by e-cigarette smoke extract (eCSE) and cytoplasmic localization were confirmed via RT-qPCR. Its effects on cancer-associated phenotypes including proliferation, ROS detoxification, resistance to apoptosis, migration, cytoskeletal disorganization, and nuclear remodeling were assessed through overexpression and siRNA-mediated knockdown in A549 and BEAS-2B cells. Results: Acute eCSE exposure induced a biphasic, dose-dependent increase in VALT1 expression, accompanied by enhanced proliferation, ROS detoxification, apoptosis resistance, migration, cytoskeletal disorganization, and nuclear remodeling in A549 cells. VALT1 overexpression reproduced these phenotypes in both cell lines without eCSE treatment, whereas knockdown attenuated them. VALT1 promoted survival under cytotoxic stress in A549 but not BEAS-2B cells. Conclusions: These findings support an active role for VALT1 as an e-cigarette vapor-upregulated transcript that contributes to its phenotypic readout and enhances cellular survival under extracellular chemical stress—thereby aggravating tumorigenic phenotypes even in the absence of mutations that contribute to malignant transformation. Full article

(1) Background: Swine hepatitis E (SHE) is an emerging zoonotic disease caused by the swine hepatitis E virus (SHEV). The open reading frame 3 (ORF3) protein is a recognized virulence factor of SHEV. Jaundice, the typical clinical sign of SHE, primarily results from disruptions in bile production, secretion, and excretion. However, the mechanism by which SHEV ORF3 influences bile metabolism remains unclear. (2) Methods: Building on our previous work involving adenovirus-mediated overexpression of genotype IV SHEV ORF3 in HepG2 cells and subsequent high-throughput lncRNA/transcriptome sequencing, this study performed KEGG enrichment analysis on differentially expressed lncRNAs. Candidate lncRNAs were validated via qRT-PCR. Cis-regulated target genes were predicted by integrating differentially expressed mRNA data. Furthermore, AlphaFold 3.0 was employed to analyze the molecular binding sites between lncRNA UBC (MSTRG.6881.4) and its target, UBC protein. (3) Results: We identified three lncRNAs associated with the bile secretion pathway (ko 04976) in HepG2 cells expressing genotype IV SHEV ORF3, which were further confirmed by qRT-PCR: lncRNA UBC (MSTRG.6881.4), lncRNA UBC (MSTRG.6881.9), and lncRNA UBC (MSTRG.6881.12). Bioinformatics prediction suggested six lncRNA-mRNA regulatory networks involved these lncRNAs and two downregulated UBC mRNA transcripts (ENST00000540700 and ENST00000536769). Molecular docking indicated that nucleotides 395U and 41C of lncRNA UBC (MSTRG.6881.4) could potentially bind to residues 82Lys, 88Thr, and 90Thr of the UBC protein, with predicted binding energies ranging from −4.73 to −0.75 kcal/mol. (4) Conclusions: The successful identification of bile secretion-related lncRNAs, coupled with the prediction of their regulatory networks and molecular interaction sites, has advanced our understanding of SHEV ORF3 function and the pathogenesis of SHEV infection. Full article

Osmanthus fragrans, a fragrant plant native to China, is extensively utilized in the food and cosmetics industries. However, its optimal harvest period spans only 2–3 days, restricting industrial utilization. Long non-coding RNAs (lncRNAs) have emerged as key regulators of plant growth, yet their roles in O. fragrans petal opening and senescence remain unexplored. Here, we performed high-throughput sequencing of O. fragrans petals across six developmental stages, generating a valuable transcriptomic resource. We identified 57,860 mRNAs and 2414 lncRNAs, including 6499 differentially expressed mRNAs (DEMs) and 494 differentially expressed lncRNAs (DELs). Co-expression and WGCNA analyses revealed key modules associated with petal opening (Turquoise module) and senescence (Blue module). The Blue module, significantly correlated with the S6 senescence stage, contained hub lncRNAs novel_00098659 and novel_00077227 co-expressed with multiple transcription factors and hormone signaling components, including 10 ERFs, OfEIN3, OfJAZ, and OfMYC2. Transient overexpression of novel_00077227 in tobacco accelerated leaf senescence in a hormone-dependent manner, with significant increases in electrolyte leakage and MDA content, and reductions in chlorophyll content and antioxidant enzyme activities. qRT-PCR analysis confirmed that novel_00077227 alters the expression of tobacco homologs of predicted target genes involved in ethylene, auxin, jasmonate, and ABA signaling pathways. This study provides a valuable transcriptomic resource of senescence-associated lncRNAs in O. fragrans and offers evidence for the potential involvement of a key candidate, novel_00077227, in hormone-associated senescence regulation. These findings provide a foundation for future functional studies and potential applications in extending flower longevity. Full article

Pollen development is a complex process that is highly sensitive to environmental stresses. Abscisic acid (ABA), a key hormone mediating plant growth and stress responses, has been implicated in the regulation of sexual reproduction, especially pollen development, yet its precise regulatory role remains unclear. This study investigated the effects of exogenous ABA on Arabidopsis thaliana pollen development and function through integrated phenotypic, cytological, and transcriptomic approaches. ABA treatment specifically impaired pollen function by reducing germination rates and inhibiting pollen tube elongation, which resulted in shortened siliques and decreased seed set, without affecting pollen morphology or viability. Transcriptome analysis of mature anthers revealed a transient and time-dependent transcriptional response, with the number of differentially expressed genes (DEGs) peaking at 8 h post-ABA treatment and markedly declining by 22 h. These DEGs were enriched in stress-response pathways (e.g., salt, cold, and dehydration), hormone signaling, and carbohydrate metabolism. Moreover, we identified 25 differentially expressed transcription factors and 16 pollen development and function-related genes, highlighting their key roles in ABA-mediated regulation. In parallel, 146 differentially expressed lncRNAs (DELs) were identified, which formed 144 cis-regulatory pairs with genes involved in ABA response and pollen tube growth, with their predicted targets enriched in pathways such as hormone and MAPK signaling, carbohydrate metabolism and stress response. Trans-regulatory analysis further revealed that these DELs co-expressed with DEGs in modules enriched for stress response, pollen development, and tube growth pathways. Notably, key pollen function genes showed strong co-expression with DELs, indicating that lncRNAs participate in ABA-induced transcriptional reprogramming that shifts metabolic resources from growth to defense, thereby suppressing pollen germination and tube elongation. Together, these findings elucidate a coordinated regulatory network involving mRNAs, lncRNAs and transcription factors roles in modulating ABA responses during pollen/anther development. Full article

Accumulating studies have identified the pivotal role of long non-coding RNAs (lncRNAs) in participating in host–virus interactions during virus infections. However, the regulatory roles of lncRNAs in influenza A virus (IAV) infection are still not fully elucidated. In this study, using high-throughput sequencing, we comprehensively compared the expression profiles of lncRNAs and mRNAs in mouse lungs infected either with the nonpathogenic parental (SDL124) H7N9 virus or its moderately pathogenic mouse-adapted (S8) variant. A total of 7636 significantly differentially expressed (SDE) lncRNAs were obtained in the S8-infected group compared to the mock group. As for the SDL124 group, 1042 SDE lncRNAs were identified. Subsequently, the mRNAs co-expressed with SDE lncRNAs were subjected to functional annotation and pathway enrichment analysis. The results indicated that the target mRNAs regulated by the S8 virus were mainly enriched in various immunological processes and exhibited a strong correlation with inflammatory-related signaling pathways. Moreover, 12 lncRNAs and 10 mRNAs co-expressed with SDE lncRNAs were selected and successfully verified by RT-qPCR. Among these lncRNAs, NONMMUG032982.2 and NONMMUG032328.2 exhibited strong antiviral activity against IAV. Additionally, these two lncRNAs were chosen for further in-depth bioinformatics analysis, including transcription factor prediction, coding capacity assessment, genomic location, construction of secondary structure, and prediction of potential interacting proteins. Taken together, these findings provide a cluster of lncRNAs probably associated with the virulence of IAV in mice and shed light on the anti-IAV effects of two functional lncRNAs, establishing a molecular foundation for further exploring the regulatory mechanisms of lncRNAs in IAV infection. Full article

Long non-coding RNAs (lncRNAs) are transcripts constituted of more than 200 nucleotides that have been associated with the regulation of different biological processes by modulating the expression of key genes. In horses, evidence suggests that lncRNAs play a role in female reproductive fitness, yet their functional implications remain poorly characterized. The objective of this study was to investigate potential DNA:RNA triplex interactions between the promoter regions of fertility-related genes and lncRNAs transcribed from non-coding loci located within ±50 kb of these genes. By doing so, we aimed to elucidate the regulatory mechanisms underlying fertility in Pura Raza Española (PRE) horses. The observed distances (1.2–49.8 kb) were consistent with cis-acting lncRNAs. Furthermore, genomic context and structural accessibility analyses revealed that some predicted DNA-binding sites reside within CpG islands. This strategic localization in active promoter regions points toward a regulatory mechanism where lncRNAs may modulate transcriptional activity via triplex formation. Our results provide a concrete set of biologically plausible lncRNAs within fertility-associated genomic regions, representing targets for further functional validation and potential applications in genomic improvement strategies. Full article