Search Results (2,976)

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

Background/Objectives: Non-coding RNAs provide new chances of targeting multiple oncogenic pathways. Many long non-coding RNAs (lncRNAs) are being characterized as relevant in cancer initiation, progression, and recurrence. Mitochondrial D-loop 1 antisense lncRNA (MDL1AS) is a novel lncRNA that might be important in cancer development, so the aim of this project was to understand its function in differently differentiated cancer cells. Methods: The effects of MDL1AS downregulation on the cellular behavior of NTERA2 and SH-SY5Y cell lines were studied. Results: MDL1AS reduction inhibited oxidative phosphorylation in NTERA2 cells and induced neuritic differentiation in SH-SY5Y cells. This downregulation also produced a strong DNA damage response (DDR) and an increased apoptotic signature by RNAseq analysis, and decreased proliferation in both cell lines. It also decreased radiosensitivity in NTERA2 cells but not in SH-SY5Y. Conclusions: These results suggest that MDL1AS reduction can modulate radiosensitivity, metabolism, and differentiation in a cell type-specific manner. Furthermore, MDL1AS may constitute a predictive biomarker and a molecular target for new therapies. Full article

Grafted plants carrying DNA from both species are prone to new phenotypes. Specific long non-coding RNA (lncRNA) sequences are known to play roles in the formation and development of grafted plants. However, the roles of lncRNAs in phenotypic variation in grafts between peach and apricot remain unexplored. In this study, mixed tissues (leaves, buds and fully bloomed flowers) of peach branches from heterografts between apricot/peach (A/P) and peach/apricot (P/A) and homografted peach (SP) were collected for transcriptome sequencing. The differentially expressed genes (DEGs) and lncRNAs (DElncRNAs) between A/P and P/A were identified as candidates mediating the formation of divergent traits. Compared with SP, 1115 and 624 DEGs were detected in A/P and P/A, respectively. There were 173 DEGs shared between A/P and P/A, whereas the transcripts of 942 genes were specifically altered in A/P and 451 DEGs were specific to P/A. There were 29 DElncRNAs in A/P and 26 DElncRNAs in P/A, of which, 21 DElncRNAs were specific to A/P and 18 were specific to P/A. The biological functions of the DEGs and DElncRNAs were predicted via GO and KEGG enrichment analyses. A total of 24 co-expressed ‘lncRNA-mRNA’ pairs were identified, including 14 ‘lncRNA-mRNA’ pairs in A/P and 10 ‘lncRNA-mRNA’ pairs in P/A. The ‘MSTRG.17020.2-XM_007210198-2’ pair potentially participates in aminoacyl biosynthesis, and the ‘MSTRG.8395.1-XM_007217967.2’ pair may regulate galactose metabolism. The lncRNA MSTRG.6365.3 may regulate defense response through altering the levels of XM_020556240.1 and XM_020556234.1. These findings provide valuable insights into the molecular mechanisms underlying grafting-induced differential trait formation and establish a foundation for further research on the functional roles of ‘lncRNA-mRNA’ pairs in fruit tree grafting systems. Full article

Background/Objectives: Schistosomiasis is a neglected tropical disease affecting >200 million people worldwide. Praziquantel is the sole recommended drug against Schistosoma mansoni; however, it lacks activity against juvenile forms and cannot prevent reinfection. Thus, there is an urgent need to identify novel therapeutic targets. Long noncoding RNAs (lncRNAs) are known to regulate various biological processes in S. mansoni, including parasite pairing and fertility; therefore, screening for novel lncRNAs could reveal new potential targets. Methods: We compiled all publicly available RNA-seq data from the Sequence Read Archive (SRA) and performed a hierarchical transcriptome assembly using the multi-sample assembler Ryūtō, combined with version 10 of the S. mansoni genome. We applied HOMER for peak-calling and identification of histone marks and used weighted gene co-expression network analysis (WGCNA) to infer putative functions of lncRNAs in sexual dimorphism. Results: Using a robust pipeline, we identified 10,170 novel lncRNA genes comprising 16,990 novel lncRNA transcripts, including 8783 intergenic, 7918 antisense, and 289 intronic lncRNA transcripts. Most (78.7%) have histone regulatory marks (H3K4me3, H3K27me3, H3K27ac, or H4K20me1) near their transcription start sites, indicating potential expression regulation. Comparing male and female samples, we identified 1991 differentially expressed genes (FDR < 5%, |log₂FC| ≥ 1.5), including 296 known lncRNAs and 339 novel lncRNAs. WGCNA identified hub lncRNAs within co-expression modules, and Gene Ontology enrichment analyses (FDR ≤ 5%) suggest that these lncRNAs are involved in cell differentiation and morphogenesis pathways. Conclusions: We provide a comprehensive catalog of S. mansoni lncRNAs. These findings offer opportunities to discover potential new therapeutic targets, advancing the future development of anti-schistosome therapies. Full article

DNA methylation is a fundamental epigenetic regulator in hepatocellular carcinoma (HCC). However, a key paradox remains: how do ubiquitously expressed enzymes like DNMTs and TETs achieve locus-specific regulation without intrinsic sequence specificity? This review aims to elucidate the “lncRNA–DNA methylation axis,” examining how long non-coding RNAs (lncRNAs) confer specificity and plasticity to methylation machinery. We synthesized current literature focusing on the structural mechanisms (e.g., R-loops, DNA:RNA triplexes) by which lncRNAs interact with DNMTs and TETs. We further analyzed the bidirectional regulation between lncRNAs and methylation enzymes and their impact on HCC phenotypes. lncRNAs function as modular scaffolds and guides, directing methylation machinery to specific genomic loci. Rather than binary switches, they act as an “epigenetic rheostat,” fine-tuning methylation intensity to balance stability with plasticity. Crucially, a reciprocal feedback loop exists: aberrant DNA methylation suppresses tumor-suppressive lncRNAs, which in turn unleashes DNMT activity, locking cells into a malignant state. This axis drives proliferation, metastasis, metabolic reprogramming, and therapeutic resistance. The lncRNA–DNA methylation axis is a central determinant of epigenetic heterogeneity in HCC. Moving beyond descriptive cataloging to a mechanistic understanding of this network offers new perspectives for developing targeted epigenetic therapies and biomarkers. Full article