Single-cell RNA sequencing highlights the unique tumor microenvironment of small cell neuroendocrine cervical carcinoma

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 6, 2025

Small cell neuroendocrine cervical carcinoma is a highly aggressive tumor characterized by early metastasis, high recurrence rate, and poor prognosis. This study represents the first instance of single-cell sequencing conducted on small cervix worldwide. Analysis gene expression regulatory networks revealed that transcription factor TFF3 drived up-regulation ELF3. Furthermore, our findings indicated marker genes associated with differed from those observed in lung, intestine, liver within GEO database, suggesting tissue-specific origins for these malignancies. Overall, this addresses significant research understanding vivo provides valuable insights guiding radiotherapy, chemotherapy, targeted therapy.

Язык: Английский

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Integrated analysis of ATAC-seq and RNA-seq reveals the chromatin accessibility and transcriptional landscape of immunoglobulin a nephropathy

Clinical Immunology, Год журнала: 2025, Номер 272, С. 110432 - 110432

Опубликована: Янв. 21, 2025

Язык: Английский

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Structural Variation Analysis in the samd3/elf3 Intergenic Region of the Barred knifejaw (Oplegnathus fasciatus) and the Development of Molecular Marker for Efficient Sex Identification

Marine Biotechnology, Год журнала: 2025, Номер 27(1)

Опубликована: Фев. 1, 2025

Язык: Английский

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Multi-omics integration analysis of the amino-acid metabolism-related genes identifies putatively causal variants of ACCS associated with hepatitis B virus-related hepatocellular carcinoma survival

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 18, 2025

Amino acid metabolism (AAM) reprogramming plays a crucial role in hepatocellular carcinoma (HCC), but its genetic pathophysiology was not fully elucidated. Therefore, we employed summary data-based Mendelian randomization (SMR) approach to identify putative causal effects of the AAM-related genes on hepatitis B virus (HBV)-HCC survival via integrating multi-omics data. Multivariate Cox proportional hazards regression models were used evaluate associations between variants and overall (OS) HBV-HCC patients (n = 866). Next, developed pathway-specific risk score (GRS) comprising AAM pathway. Subsequently, SNPs prioritized using SMR by OS data with expression quantitative trait loci (eQTLs) DNA methylation QTLs (mQTLs) from blood, as well eQTLs liver tissues. We identified 23 independent associated OS, GRS derived significant predictor OS. The addition significantly improved predictive performance 5-year model (AUC increased 72.04% 84.67%, P < 0.001). By mQTLs variant rs2074038 across ACCS expression, methylation. Furthermore, integration eQTL revealed that levels worse Mechanistically, bioinformatics annotation luciferase reporter assays further demonstrated contributes progression allele-specific regulation expression. This study novel functional SNP poor survival, likely mediated These findings suggest is potential therapeutic target highlight need for validation clinical settings.

Язык: Английский

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Versatile roles of Annexin A4 in ccRCC: impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment

iScience, Год журнала: 2025, Номер 28(4), С. 112198 - 112198

Опубликована: Март 12, 2025

Язык: Английский

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Application of genomic tools to study and potentially improve the upper thermal tolerance of farmed Atlantic salmon (Salmo salar)

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Март 24, 2025

Abstract Background The Atlantic salmon ( Salmo salar ) aquaculture industry must mitigate the impacts of rising ocean temperatures and increased prevalence/severity marine heat waves. Therefore, we investigated genetic architecture gene expression (transcriptomics) responsible for determining a salmon’s upper thermal tolerance. Results A genome-wide association study (GWAS) was conducted using fin clips from previous incremental maximum (IT Max challenge n = 251) North American 50 K SNP chip. IT highly polygenic trait with low/moderate heritability (mean SNP-based h 2 0.20 pedigree-based 0.25). Using data same fish, separate GWAS assessed thermal-unit growth coefficient (TGC). Five significant SNPs were detected on chromosomes three five, high estimates calculated TGC measured as fish grew 12 to 20 °C 0.62 0.64). RNA-seq analyses liver samples 5–6 family -1 temperature collected four most least tolerant families at 10 also used provide insights into potential mechanisms modulating this species’ Between top bottom families, 347 175 differentially expressed transcripts (FDR-adjusted p < 0.01; fold-change ≥|2.0|) identified °C, respectively. GO term enrichment analysis revealed unique responses elevated between rankings (e.g., ‘blood coagulation’, ‘sterol metabolic process’ ‘synaptic neuromuscular junction’). qPCR further confirmed differences pertaining cholesterol metabolism lpl ), inflammation epx , elf3 ccl20 apoptosis htra1b htra2 anxa5b angiogenesis angl4 pdgfa nervous system processes insyn2a kcnj11l stress serpinh1b-1 serpinh1b-2 ). Three (i.e., ppp1r9a gal3st1a f5 located in close proximity (± 120 kbp) near-significant GWAS. Interestingly, have putative neurological functions, while regulates blood coagulation. Conclusions These several biomarkers tolerance that could prove valuable helping develop more temperature-tolerant fish. Further, our supports reports has species, suggests is heritable.

Язык: Английский

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The ELF3-TRIM22-MAVS signaling axis regulates type I interferon and antiviral responses

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

ABSTRACT Activation of the innate immune response is essential for host cells to restrict dissemination invading viruses and other pathogens. Proteins belonging tripartite motif (TRIM) family are key effectors in antiviral immunity. Among these, TRIM22, a RING-type E3 ubiquitin ligase, has been recognized as significant regulator pathogenesis various diseases. In present study, we identified TRIM22 critical modulator mitochondrial signaling protein (MAVS) activation. Loss function led reduced production type I interferons (IFNs) viral infection such influenza A virus (IAV) or vesicular stomatitis (VSV), thereby facilitating replication. Mechanistically, was found enhance retinoic acid-inducible gene (RIG-I)-mediated through catalysis Lys63-linked polyubiquitination MAVS, which, turn, activated TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) pathway, driving IFN-β production. Additionally, shown inhibit assembly MAVS-NLRX1 inhibitory complex, further amplifying responses. Our findings also demonstrated that RNA upregulated expression via nuclear translocation ELF3, transcription activates expression. This loop underscores role modulating IFN providing insights into host’s defense mechanisms. research highlights potential targeting ELF3-TRIM22-MAVS axis therapeutic strategy enhancing immunity preventing infections. IMPORTANCE Interferon (IFN)-mediated responses crucial against foreign pathogens regulated by pathways. The family, its multifaceted roles regulation defense, plays part this process. our explored important helped regulate We enhances (MAVS), which producing interferons. Interestingly, discovered increases after an infection, due moved nucleus activate transcription. created feedback strengthens pathway. By uncovering these mechanisms, aimed understanding how system works provide could lead innovative therapies.

Язык: Английский

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Enhanced Effects of Polystyrene Nanoplastics and Imidacloprid on Organ Damage in Loaches(Misgurnus Anguillicaudatus): Disrupted Gene Expression Leads to Imbalance in Lipid Metabolism

Опубликована: Янв. 1, 2025

Язык: Английский

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Current concepts of the crosstalk between lncRNA and E2F1: shedding light on the cancer therapy

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Июль 25, 2024

Long noncoding RNAs (lncRNAs) constitute a distinctive subset of RNA molecules with limited protein-coding potential, which exert crucial impacts on various biological activities. In the context cancer, dysregulated lncRNAs function as essential regulators that affect tumor initiation and malignant progression. These serve competitive endogenous (ceRNAs) through sponging microRNAs regulating expression targeted genes. Moreover, they also directly bind to RNA-binding proteins, can be integrated into complex mechanistic network. E2F1, an extensively studied transcription factor, mediates multiple behaviors by cell cycle progression, metastasis, therapeutic response. Emerging evidence suggests play pivotal role in E2F1 pathway. This review aims elucidate intricate gene regulatory programs between cancer We elaborate distinct networks involved emphasizing potential lncRNAs/E2F1 axes promising targets for therapy. Additionally, we provide novel perspectives current evidence, limitations, future directions targeting human cancers. Fully deciphering network lncRNA/E2F1-mediated mechanisms could facilitate translation findings clinical course, such efforts ultimately significantly improve prognosis patients.

Язык: Английский

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Versatile roles of Annexin A4 in ccRCC: impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 3, 2024

Abstract Clear cell renal carcinoma (ccRCC) is the most prevalent type of malignant disease and characterized by dismal prognosis in metastasized setting. Invasive growth cancer cells relates to high levels compressive forces translating relevant damage plasma membrane. However, functional implications protein machineries required for membrane repair ccRCC are not yet completely elucidated. Given membrane-associated localization large family annexin proteins, we aimed a global annotation which led identification ANXA4 selectively expressed ccRCC. Interestingly, showed context-dependent distinct patterns including as well nuclear compartment/nuclear We investigated role employing genetic titration studies (knockdown, CRISPR/Cas9 knockout overexpression) identified impaired acute invasive capability conditions reduced expression. Utilizing computational segmentation tumor microenvironment (TME) samples revealed that low tumors exhibited TME composition compared cases. higher infiltrating lymphocytes accompanied increased deposition acellular extracellular matrix. Further transcriptomic analysis demonstrated major alterations transcriptional signatures related epithelial-mesenchymal transition (EMT) immune signaling. Transcription factor enrichment further validation ELF3 one central regulator properties. Our integrative approach molecular analyses with advanced histopathological uncovered novel roles modulating repair, regulation, shaping cellular microenvironment.

Язык: Английский

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