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Results for “Gene Expression Profiling”

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PubMed2025

Inhibitor of DNA binding-1 is a key regulator of cancer cell vasculogenic mimicry.

Solid tumours routinely access the blood supply by promoting endothelium-dependent angiogenesis; but tumour vasculature can also be formed by cancer cells themselves via vasculogenic mimicry (VM). Investigation of the gene expression profile during the early stages of VM formation by MDA-MB-231-LM2 breast cancer cells identified the transcriptional regulator inhibitor of DNA binding 1 (ID1) to be elevated ~ 10-fold within the first 2 hours. This role for ID1 in promoting VM was supported by ID1 genetic knockdown or chemical inhibition interrupting VM formation by MDA-MB-231-LM2 (breast) and BxPC-3 (pancreatic) cancer cells. More specifically, reducing ID1 lowered cancer cell expression of endothelial cell genes (e.g. CDH5, TIE2) and production of pro-angiogenic proteins (e.g. VEGF, CD31, MMP9 and IL-8). In silico analysis of MDA-MB-231 cells engrafted into mice identified elevated ID1 expression in cancer cells that had metastasised to the lungs or liver, and an enrichment of pro-angiogenic genes. Additionally, Id1 knockdown in 4T1.13 murine breast cancer cells demonstrated reduced tumour growth and metastasis in vivo. Taken together, this study further implicates ID1 in a vascular program within cancer cells that supports disease progression.

Humans↗

PubMed2026

Transcriptomic analysis reveals the molecular mechanisms underlying the inhibition of Mytilus edulis attachment by biofouling control agents.

This study combined acute toxicity assays, phenotypic quantification, and transcriptomic profiling to systematically investigate the inhibitory effects and molecular regulatory mechanisms of a novel alkylamine-based antifouling agent on survival, byssus secretion, and attachment behavior of juvenile Mytilus edulis. The 96 h-LC50 of the agent to juvenile M. edulis was 8.84 mg/L, and 10 mg/L of the agent completely inhibited mussel attachment within 24 h, significantly reducing byssal thread number, length, and diameter while increasing detachment frequency, resulting in irreversible attachment failure. Transcriptomic analysis identified 2746 differentially expressed genes, which were mainly enriched in pathways including signal transduction, immune defense, stress response, cytoskeleton organization, and protein binding. KEGG and GSEA enrichment revealed that the antifouling agent activated the MAPK stress signaling pathway, disturbed transcriptional regulation, and impaired intracellular homeostasis and cytoskeletal stability, thereby synergistically suppressing the expression of key byssal protein genes including mfp-1 and mfp-3 and ultimately blocking byssus synthesis and adhesion. This study clarifies the multi-pathway molecular mechanism underlying antifouling agent-induced attachment inhibition in M. edulis, and provides core molecular targets and theoretical support for developing efficient, specific antifouling activity, and potentially applicable marine antifouling technologies.

Animals↗

PubMed2026

Single-cell transcriptomics reveals that air-liquid interface culture promotes goblet cell differentiation and inhibits glycolysis in organoid cell monolayers.

Faithfully recapitulating the cellular heterogeneity of the intestinal epithelium is essential when using organoid models. Air-liquid interface (ALI) culture has been shown to promote secretory cell differentiation, but its impact on gene expression in each epithelial cell type remains unclear. In this study, we used single-cell RNA sequencing (scRNA-seq) to characterize the cellular heterogeneity of rabbit cecum-derived organoid monolayers grown under immerged or ALI conditions. We then compared these organoid cell type-specific gene expression profiles to a scRNA-seq atlas of the rabbit cecal epithelium in vivo. We selected the rabbit model notably because, unlike mice, it possesses BEST4+ epithelial cells, a newly discovered subset of mature absorptive cells. Our analysis revealed a high degree of transcriptomic similarity between in vivo and organoid-derived stem and transit-amplifying cells. ALI culture markedly enhanced the differentiation of the secretory lineage, especially goblet cells, whose transcriptome closely resembled that of in vivo goblet cells. Furthermore, ALI was the only condition allowing the detection of enteroendocrine cells. BEST4+ cells, however, were absent from organoids in immerged or ALI conditions despite their presence in vivo. In addition, ALI culture led to a consistent downregulation of hypoxia and glycolysis-associated genes across all cell types, which suggests a metabolic shift likely driven by increased oxygen availability in ALI conditions. Cell-cell communication analyses further indicated that ALI more closely mirrored in vivo patterns than immerged condition. Altogether, these results demonstrate that ALI culture allows for better recapitulation of the in vivo cellular heterogeneity and molecular signatures of the intestinal epithelium.NEW & NOTEWORTHY Using single-cell RNA sequencing, this study shows that air-liquid interface (ALI) culture enhances secretory lineage differentiation of intestinal organoid cell monolayers and improves transcriptomic similarity to the native epithelium. ALI reduced hypoxia-associated gene expression and better recapitulates in vivo-like cell-cell interactions, supporting its value for modeling intestinal epithelial heterogeneity in organoids.

Animals↗

PubMed2026

Hope is linked with more favorable tumor molecular signatures in serous ovarian cancer.

INTRODUCTION: Hope has been associated with improved quality of life and lower mortality in cancer, but the underlying biological mechanisms are poorly characterized. We previously reported that hope was associated with less inflammation and more normalized diurnal cortisol pre-treatment among women with ovarian cancer. We also reported associations of socio-environmental factors with pro-metastatic processes. Here, we used genome-wide transcriptional profiling to quantify associations between hope and tumor molecular signatures reflecting invasiveness, inflammation, and cellular immunity. METHOD: Participants were 74 women with serous ovarian cancer who provided demographic information and completed surveys pre-surgery. Hope was assessed using a face-valid item from the Center for Epidemiological Studies Depression Scale (CES-D). Depression was assessed using the full CES-D without the hope item. Illumina HT12 microarrays were used to assay tumor RNA, and associations between hope and tumor gene expression were quantified, adjusting for depression, age, BMI, grade, and stage. RESULTS: Adjusting for covariates, hope was associated with multiple favorable differences in RNA expression, including lower levels of mesenchymal differentiation (p = 0.008) and pro-inflammatory gene regulation (NF-κB: p < 0.001; IRF1: p = 0.024; STAT: p = 0.018), elevated epithelial differentiation (p = 0.011), and elevated activity of the IRF7 transcription factor which promotes cellular immunity (p = 0.016). CONCLUSIONS: These data suggest that hope is associated with an ovarian tumor gene expression profile characterized by reduced epithelial-mesenchymal transition (EMT) and inflammatory activity, and increased activity of a transcription factor promoting cellular immunity. These findings highlight potential biological implications of a resilience factor such as hope, but need replication with more robust assessments of hope.

Epithelial mesenchymal transition↗

PubMed2025

Transcriptome and metabolome profiling of the medicinal plant Dictamnus dasycarpus reveal key genes involved in quinoline alkaloids biosynthesis and limonoids biosynthesis.

BACKGROUND: As a member of Rutaceae family, Dictamnus dasycarpus Turcz. represents a prominent medicinal plant and economically valuable crop in traditional Chinese medicine, and is renowned for its therapeutic efficacy in treating dermatological conditions. The pharmacological activity of this species primarily stems from quinoline alkaloids and limonoids, which predominantly accumulate in the taproots. These bioactive compounds serve as critical determinants of both medicinal quality and crop yield. Nevertheless, the molecular mechanisms governing their dynamic accumulation patterns in D. dasycarpus taproots remain uncertain, and the fundamental biochemical basis underlying this process has yet to be elucidated. RESULTS: Metabolomic and transcriptomic analyses were carried out to investigate metabolites and gene expression during the development of D. dasycarpus taproots. The differentially accumulated secondary metabolites (DAMs) mainly included quinoline alkaloids and limonoids, and the accumulation of total alkaloids and total limonoids primarily occurred during 2- and 4-year-old. The differentially expressed genes (DEGs) are related to Glycolysis/Gluconeogenesis, Phenylalanine, tyrosine and tryptophan biosynthesis, Tryptophan metabolism, Terpenoid backbone biosynthesis, Sesquiterpenoid and triterpenoid biosynthesis, which had a close relationship with the accumulation of quinoline alkaloids and limonoids. Furthermore, we identified that some CYP450s, acetyltransferase, isomerase, 2-ODDs and others may play an important role in the process of producing quinoline alkaloids and limonoids. CONCLUSION: These results elucidated the molecular mechanisms and metabolic changes underlying the dynamic accumulation process occurring in the taproots of D. dasycarpus. These findings provide a theoretical basis for the planting and harvesting of D. dasycarpus.

Limonins↗

PubMed1995

Growth and differentiation proceeds normally in cells deficient in the immediate early gene NGFI-A.

NGFI-A (also known as EGR-1, zif/268, and Krox-24) is a zinc finger transcription factor induced in many cell types by a variety of growth and differentiation stimuli. To determine if NGFI-A plays a requisite role in these processes, we used homologous recombination to mutate both alleles of NGFI-A in embryonic stem (ES) cells and examined its effect on growth and differentiation. We find that ES cells lacking NGFI-A exhibit similar growth rates and serum-induced gene expression profiles compared to wild-type parental cells. They are capable of differentiating into neurons, cardiac myocytes, chondrocytes, and squamous epithelium. Chimeric mice were generated from targeted ES cells, and their progeny were crossed to produce homozygous mutant mice. Growth and histological analyses of mice lacking NGFI-A confirm the finding in ES cells that NGFI-A is not required for many of the processes associated with its expression and suggest that the function of NGFI-A is either more subtle in vivo or masked by redundant expression provided by other gene family members such as NGFI-C, Krox-20, or EGR3.

Animals↗

PubMed2025

Spatial transcriptomic analysis of mouse parathyroid gland cells expressing an activating variant of Gcm2.

Glial cells missing 2 (GCM2) is an essential transcription factor for the development of parathyroid glands. Germline GCM2 variants that repress or enhance transcriptional activity predispose a subset of patients to hypoparathyroidism or hyperparathyroidism, respectively. A recurrent germline heterozygous activating missense variant of GCM2, p.Y394S has been identified in some patients with primary hyperparathyroidism. A genetically engineered knock-in mouse model of this variant corresponding to p.Y392S in the mouse Gcm2 gene (Gcm2 +/Y392S) did not show obvious parathyroid tumors. However, in GCM2-binding site mediated luciferase reporter assays in HEK293 cells, the mouse and the human variant both exhibited enhanced transcriptional activity. Therefore, we assessed the effect of this variant on gene expression in vivo in parathyroid glands from Gcm2 +/Y392S and WT mice. Using the 10x Genomics Visium platform, spatially resolved transcriptomic analysis was performed on formalin-fixed and paraffin-embedded (FFPE) tracheal tissue sections of Gcm2 +/Y392S and WT mice to capture RNA from parathyroid glands together with other cell types in the tissue sections. Transcriptome sequence data analysis detected 8 different clusters in the tissue sections based on similarity of gene expression profiles. Cluster-1, which contained parathyroid gland cells expressing Pth and Gcm2, was further evaluated for transcripts that were differentially expressed more than 2-fold in Gcm2 +/Y392S compared to WT. Increased transcript level of Lgals3 (galectin-3) was seen in Gcm2 +/Y392S parathyroid gland cells which is among markers of parathyroid carcinoma. Galectin-3 protein was detected in available FFPE human parathyroid samples of patients with germline heterozygous activating GCM2 variants, p.Y394S (n = 4/10) or p.L379Q (n = 2/2). These results indicate a potential for growth and malignancy of parathyroid glands expressing GCM2 variants. The transcriptomic data of mouse parathyroid gland cells generated in this study can serve as a valuable resource for investigating genes and pathways in normal or abnormal parathyroid gland growth and physiology.

GCM2, gene↗

PubMed2026

Fibrotubular Tumors of the Thyroid: An Emerging Thyroid Neoplasm Characterized by Distinctive Morphology and Recurrent OCLN::PRKCI Gene Fusions Spanning the Adenoma-Carcinoma Spectrum.

The histopathologic and genomic landscape of thyroid tumors is well characterized, although new genetic alterations and tumor types are being described. We present 2 cases of thyroid tumors originating from follicular cells that had highly unusual and distinct morphologic features and carried an OCLN::PRKCI gene fusion. These tumors were well circumscribed, encapsulated, and composed of irregularly shaped tubular and follicular structures surrounded by layers of distinct fibrocollagenous basement membrane material positive for type IV collagen and laminin; they showed no definitive nuclear features of papillary carcinoma. Importantly, whereas one of the tumors had no invasive growth, the other demonstrated tumor capsule invasion, compatible with the adenoma-carcinoma spectrum seen in thyroid follicular and oncocytic tumors. Gene expression profiles of these tumors differed from those of common types of papillary thyroid carcinoma. The unusual and reproducible histopathologic characteristics and unique molecular profiles of these tumors support their designation as a distinct type of thyroid neoplasm that exists in noninvasive and invasive forms and, therefore, can be designated as fibrotubular adenoma and carcinoma. Recognition of this distinct entity is important for improving diagnostic accuracy and avoiding overtreatment of this likely indolent type of thyroid neoplasia.

Humans↗

PubMed2026

PDZ-binding kinase promotes ovarian cancer cell proliferation and invasion via CCNB1 regulation.

BACKGROUND: Ovarian cancer is one of the most lethal gynecological malignancies, characterized by late diagnosis, frequent recurrence, and high mortality. PDZ-binding kinase (PBK), a serine/threonine kinase of the mitogen-activated protein kinase kinase (MAPKK) family, has been implicated in the tumorigenesis of multiple cancers, yet its role in ovarian cancer remains incompletely characterized. This study aimed to investigate the effect of PBK on the proliferation and invasion of ovarian cancer cells. METHODS: The expression of PBK and cyclin B1 (CCNB1) in normal ovarian tissues and ovarian cancer tissues was analyzed using online databases including Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Kaplan-Meier Plotter. Clinical tissue specimens were collected to detect the expression of PBK and CCNB1 by immunohistochemistry. Quantitative real-time polymerase chain reaction (PCR) was performed to detect PBK messenger RNA (mRNA) expression levels in clinical specimens and cell lines. Western blot was used to detect PBK protein expression in ovarian cancer cell lines. ES2 and A2780 cells with higher PBK expression were selected to construct PBK knockdown cell lines using lentiviral interference vectors. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) assay were performed to explore the effect of PBK knockdown on cell proliferation. Transwell assay was used to investigate the effect on cell invasion. The Cancer Genome Atlas (TCGA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized to analyze PBK-related pathways and predict CCNB1 as the gene most closely related to PBK. RESULTS: PBK was significantly overexpressed in ovarian cancer tissues and cell lines compared with normal controls, and high PBK expression was associated with poor overall survival (OS) and progression-free survival (PFS). Knockdown of PBK expression inhibited the proliferation, colony formation, and invasion of ovarian cancer cells. Bioinformatics analysis revealed that CCNB1 was significantly overexpressed in ovarian cancer and high CCNB1 expression was associated with poor OS. CCNB1 was also significantly highly expressed in ovarian cancer tissues as validated by immunohistochemistry and was associated with lymph node metastasis. PBK and CCNB1 expression showed a significant positive correlation in TCGA ovarian cancer datasets. Knockdown of PBK inhibited CCNB1 expression in ovarian cancer cells. CONCLUSIONS: PBK promotes ovarian cancer cell proliferation and invasion. PBK knockdown leads to CCNB1 downregulation. These findings suggest that CCNB1 contributes to PBK-mediated oncogenic effects and identify the PBK-CCNB1 axis as a potential therapeutic target for ovarian cancer treatment.

PDZ-binding kinase (PBK)↗

PubMed2024

Exploring the prognostic landscape of oral squamous cell carcinoma through mitochondrial damage-related genes.

Oral squamous cell carcinoma (OSCC), the most prevalent form of oral cancer, poses significant challenges to the medical community due to its high recurrence rate and low survival rate. Mitochondrial Damage-Related Genes (MDGs) have been closely associated with the occurrence, metastasis, and progression of OSCC. Consequently, we constructed a prognostic model for OSCC based on MDGs and identified potential mitochondrial damage-related biomarkers. Gene expression profiles and relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Differential analysis was conducted to identify MDGs associated with OSCC. COX analysis was employed to screen seven prognosis-related MDGs and build a prognostic prediction model for OSCC. Cases were categorized into low-risk or high-risk groups based on the optimal risk score threshold. Kaplan-Meier (KM) analysis revealed significant survival differences (P < 0.05). Additionally, the area under the ROC curve (AUC) for patient survival at 1 year, 3 years, and 5 years were 0.687, 0.704, and 0.70, respectively, indicating a high long-term predictive accuracy of the prognostic model. To enhance predictive accuracy, age, gender, risk score, and TN staging were incorporated into a nomogram and verified using calibration curves. Risk scoring based on MDGs was identified as a potential independent prognostic biomarker. Furthermore, BID and SLC25A20 were identified as two potential independent mitochondrial damage-related prognostic biomarkers, offering new therapeutic targets for OSCC.

Humans↗

PubMed2026

From transcriptomic profiling to precision oncology: a bibliometric analysis of RNA sequencing in acute myeloid leukemia.

BACKGROUND: RNA sequencing (RNA-seq) has become an important tool for investigating the molecular heterogeneity of acute myeloid leukemia (AML); however, the global development and thematic evolution of this field remain inadequately characterized. OBJECTIVE: To map the global landscape of AML RNA-seq research and identify major knowledge domains, emerging themes, and temporal changes in research priorities. METHODS: Publications indexed in the Web of Science Core Collection and Scopus between January 1, 2007, and August 18, 2025, were retrieved. After database filtering, merging, and deduplication, 3,460 articles and reviews were included. CiteSpace, VOSviewer, the bibliometrix R package, and Microsoft Excel were used to analyze publication trends, collaboration networks, co-citation structures, keyword evolution, and citation bursts. RESULTS: Publication output increased steadily, accelerating after 2014. China contributed the largest number of publications (n = 547, 15.8%), whereas the United States had the highest total citation count. Major publication outlets spanned hematology, oncology, genomics, and molecular biology. Co-citation analysis identified prominent themes involving next-generation sequencing, gene mutations, KMT2A rearrangements, epigenetic dysregulation, leukemia-initiating cells, drug resistance, biomarkers, T-cell biology, and single-cell sequencing. Earlier literature emphasized sequencing technologies, gene expression profiling, and molecular alterations, whereas recent publications show increasing representation of cellular heterogeneity, single-cell transcriptomics, drug resistance, biomarker applications, immune-related research, and computational interpretation. CONCLUSION: While molecular characterization remains foundational, AML RNA-seq research has broadened to encompass increasingly prominent cellular, functional, computational, and translational dimensions. This study provides a structured overview of the field; nevertheless, bibliometric prominence should not be interpreted as direct evidence of clinical utility.

RNA sequencing↗

PubMed1994

The mRNA-phenotype of granuloma formation: CD4+ T cell-associated cytokine gene expression during primary murine listeriosis.

In murine listeriosis, elimination of bacteria and immunity to reinfection critically depend on Thy1+ CD4- cells, while cell-mediated inflammatory phenomena such as DTH and granuloma formation are mostly mediated by CD4+ T cells. In an attempt to correlate T cell phenotype and function with a particular set of cytokines produced, we examined the cytokine gene expression profile associated with the presence or absence of Thy1+, CD4+ and/or CD8+ cells in the livers of mice during a primary infection with L. monocytogenes. The presence of CD4+ cells was found to be closely associated with mRNA expression for IL-2, IL-3 and IL-4, a 5-fold increase in expression of TNF-alpha and GM-CSF and a 25-fold increase in expression of IFN-gamma and TNF-beta mRNAs, and temporally coincided with the development of granulomatous lesions. In vivo neutralization of TNF-alpha and, to a lesser extent, IFN-gamma resulted in abrogation of granuloma formation. A similar correlation between the presence of CD8+ cells and mRNA expression for any one of the cytokines studied did not exist, pointing to a qualitatively different mechanism of CD8+ T cell mediated cure of listeriosis.

Animals↗

PubMed2024

CRISPR/Cas9-driven double modification of grapevine MLO6-7 imparts powdery mildew resistance, while editing of NPR3 augments powdery and downy mildew tolerance.

The implementation of genome editing strategies in grapevine is the easiest way to improve sustainability and resilience while preserving the original genotype. Among others, the Mildew Locus-O (MLO) genes have already been reported as good candidates to develop powdery mildew-immune plants. A never-explored grapevine target is NPR3, a negative regulator of the systemic acquired resistance. We report the exploitation of a cisgenic approach with the Cre-lox recombinase technology to generate grapevine-edited plants with the potential to be transgene-free while preserving their original genetic background. The characterization of three edited lines for each target demonstrated immunity development against Erysiphe necator in MLO6-7-edited plants. Concomitantly, a significant improvement of resilience, associated with increased leaf thickness and specific biochemical responses, was observed in defective NPR3 lines against E. necator and Plasmopara viticola. Transcriptomic analysis revealed that both MLO6-7 and NPR3 defective lines modulated their gene expression profiles, pointing to distinct though partially overlapping responses. Furthermore, targeted metabolite analysis highlighted an overaccumulation of stilbenes coupled with an improved oxidative scavenging potential in both editing targets, likely protecting the MLO6-7 mutants from detrimental pleiotropic effects. Finally, the Cre-loxP approach allowed the recovery of one MLO6-7 edited plant with the complete removal of transgene. Taken together, our achievements provide a comprehensive understanding of the molecular and biochemical adjustments occurring in double MLO-defective grape plants. In parallel, the potential of NPR3 mutants for multiple purposes has been demonstrated, raising new questions on its wide role in orchestrating biotic stress responses.

Vitis↗

PubMed1990

Developmental regulation of metallothionein mRNA, zinc and copper levels in rainbow trout, Salmo gairdneri.

The metallothionein (MT) gene expression profile was followed in rainbow trout during early embryo development and in liver and gonads during the period of sexual maturation. The hepatic MT mRNA levels increase at the end of sexual maturation in both male and female rainbow trout. Although both isoforms of MT mRNA accumulate in the liver, there is a preferential increase in MT-A in the female liver. Concomitantly with this increase in MT there is a redistribution of zinc and copper to MT. In the juvenile female there is an abundance of MT mRNA in the ovaries. This is correlated to high levels of zinc in the MT fraction upon Sephadex G-75 chromatography. During ovary development the MT mRNA levels and the MT-bound zinc levels drop, with an increase in zinc being bound to high-molecular-mass proteins. At ovulation most of the zinc is found in the membrane portion upon centrifugation. In contrast to the ovaries, there are no apparent changes in either trace metal distribution or MT mRNA levels during testis development. In the developing embryo there is an increase in MT-bound copper at gastrulation. This is accompanied by an increase in both isoforms of MT mRNA. At hatch both the copper and zinc levels increase in the MT fraction, with a concomitant increase in mainly MT-A mRNA. These findings indicate that the variations in MT mRNA levels during development are closely associated with metal regulation.

Animals↗

PubMed2026

High NKAP expression predicts poor prognosis of breast cancer patients.

NF-κB activating protein (NKAP) plays important roles in various cancers, including breast cancer. However, its expression and prognosis value in breast cancer remains uncertain. Gene expression profiling interactive analysis, Human protein atlas database, and University of Alabama at Birmingham Cancer data analysis portal database were used to predict the expression and prognostic value of NKAP in breast cancer. Immunohistochemistry, quantitative real time polymerase chain reaction (qRT-PCR) and western blot were performed to detect NKAP expression. The effects of NKAP on cell proliferation, migration and drug sensitivity were investigated in MDA-MB-231 and SK-BR-3 cells. NKAP protein expression differed in breast cancer tissues and paraneoplastic tissues based on the cancer genome atlas data. The high NKAP expression was significantly correlated with a poor prognosis in breast cancer patients. The results of immunohistochemistry, western blot assay, and qRT-PCR proved that NKAP was highly expressed in breast cancer tissues compared with paraneoplastic tissues. In addition, qRT-PCR results showed that high expression of NKAP was significantly correlated with the larger tumor size and higher TNM stage. Moreover, knockdown of NKAP significantly inhibited the proliferation, migration, and enhanced drug sensitivity of MDA-MB-231 and SK-BR-3 cells. NKAP is highly expressed in breast cancer tissues, and its high expression is closely associated with poor prognosis. NKAP also promotes proliferation, migration, and inhibits drug sensitivity of breast cancer cells.

Humans↗

PubMed2026

Development and Validation of a Prognostic Signature Based on Transcription Factors Associated with Endoplasmic Reticulum Stress in Pancreatic Adenocarcinoma.

BACKGROUND: Endoplasmic reticulum stress (ER stress) plays a crucial role in influencing the malignant behaviors of various tumors. Targeting the expression or degradation of transcription factors (TFs) offers a promising avenue for cancer treatment. However, a detailed understanding of how ER stress affects TF function and their interactions remains limited. This study aims to develop a prognostic model and identify TFs associated with ER stress in pancreatic ductal adenocarcinoma (PDAC). METHODS: We obtained gene expression profiles and corresponding clinical data from The Cancer Genome Atlas (TCGA). To develop a prognostic signature, we performed several analyses, including unsupervised clustering, enrichment analysis, immune infiltration assessment, as well as univariate, LASSO, and multivariate Cox regression analyses. Four transcription factors-STAT1, IRF6, NRF1, and RXRA-were incorporated into a risk model, which was subsequently validated using the GSE dataset. Additionally, we examined IRF6 through quantitative PCR, western blotting, flow cytometry, and immunohistochemistry in vitro using pancreatic cancer cell lines and a tissue microarray. RESULTS: The high-risk group identified by the model exhibited significant associations with immune cell infiltration and poorer survival outcomes, though there was no significant correlation with tumor purity (p = 0.19). Furthermore, IRF6 downregulation in vitro was found to inhibit pancreatic cancer cell proliferation and promote apoptosis. IRF6 depletion also increased the expression of key molecules involved in ER stress at both the transcriptional and translational levels. Immunohistochemical analysis revealed marked differences in IRF6 expression between tumor and adjacent non-tumor tissues (59.29±29.88 vs. 95.22±40.80, p<0.001). CONCLUSION: This study provides evidence that the constructed risk model can effectively predict prognosis in PDAC patients. Transcription factors related to ER stress, such as IRF6, show promise as both prognostic biomarkers and potential therapeutic targets for PDAC.

Humans↗

PubMed2026

Distinct cell morphotypes of Aureobasidium melanogenum ZN exhibit differential functional profiles in promoting maize growth.

Black yeast-like fungi of the genus Aureobasidium exhibit morphological plasticity, but whether distinct cellular states within the same genetic background are associated with different plant growth-promoting functions remains unclear. Here, yeast-like cells (YL), swollen cells (SC), and chlamydospores (CH) of Aureobasidium melanogenum ZN were characterized. YL was associated mainly with siderophore production and laccase activity, SC with extracellular polysaccharide accumulation, and CH with phosphate mobilization and higher ammonia and IAA production. Whole-genome and comparative genomic analyses revealed a shared repertoire related to nutrient acquisition, auxin-associated metabolism, extracellular oxidation, and carbohydrate remodeling, with expansions in nutrient- and cell-surface-related gene families. Transcriptomic and metabolomic analyses showed distinct deployment of these capacities, with CH exhibiting broad reprogramming of tryptophan-associated, nitrogen, phosphate, central-carbon, and amino-acid metabolism. In maize, CH at the optimal inoculation concentration of 105 CFU·mL-1 produced the strongest growth promotion, increasing plant height, dry biomass, root length, root surface area, and root volume by 58.6%, 365.1%, 191.0%, 194.3%, and 222.4%, respectively. Consistent with this pronounced growth phenotype, maize root transcriptomics showed coordinated CH-induced responses involving root development, nutrient transport, redox regulation, and root-interface remodeling. Root-zone tracking showed greater short-term stability and persistence of CH. These findings identify cellular state as an important functional dimension of Aureobasidium-plant interactions and provide a basis for developing fungal inoculants with defined beneficial cellular states.

Zea mays↗

PubMed2025

An Immunosenescent CD8+ T Cell Subset in Patients with Axial Spondyloarthritis and Psoriatic Arthritis Links Spontaneous Motility to Telomere Shortening and Dysfunction.

OBJECTIVE: A pathogenetic role of CD8+ T lymphocytes in radiographic axial spondyloarthritis (r-axSpA) and other spondyloarthritis (SpA) is sustained by genome-wide association studies and by the expansion of public T cell clonotypes in the target tissues. This study investigates the migration of CD8+ T cells along with their phenotype and functions in patients with r-axSpA and psoriatic arthritis (PsA). METHODS: Peripheral blood CD8+ and CD4+ T cells were isolated from patients with r-axSpA (n = 128), PsA (n = 60), and rheumatoid arthritis (RA) (n = 74) and healthy donors (HDs) (n = 79). Transwell migration assay was performed in the presence of different chemokines. CD8+ T cell immunoprofiling and effector functions were assessed by multiparametric flow cytometry. Transcriptome signature was evaluated by RNA sequencing analysis, whereas telomere length and dysfunction were measured by reverse transcriptase-polymerase chain reaction and immunofluorescence-fluorescence in situ hybridization, respectively. RESULTS: A significantly higher number of CD8+ T cells migrating in the absence of chemokine stimuli was found in patients with SpA compared with HDs and patients with RA. This subset, producing cytotoxic (granzyme B, perforin, granulysin) and proinflammatory molecules (tumor necrosis factor), was significantly enriched in terminally differentiated (CCR7-CD45RA+) and senescent (CD28-CD57+) cells having a gene expression profile characterized by cytolytic signature and natural killer markers. Remarkably, these spontaneously migrating CD8+ T cells showed DNA damage response activation, telomere shortening, and dysfunction. CONCLUSION: These data describe a terminally differentiated CD8+ T cell subset with a senescent and cytotoxic/proinflammatory profile and an intrinsic invasive potential enriched in patients with SpA that represents a possible player in disease pathogenesis.

Humans↗