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Results for “Gene Expression Profiling”

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PubMed2026

NR3C1 Modulates Wnt Signalling to Influence the Invasiveness and Immune Features of Nonfunctioning Invasive Pituitary Adenomas.

Pituitary adenomas (PAs) are common intracranial tumours, and invasiveness in nonfunctioning invasive pituitary adenomas (NIPAs) predicts poor prognosis. The molecular mechanisms driving this phenotype remain unclear. This study explored the role of nuclear receptor subfamily 3 group C member 1 (NR3C1) in NIPA invasiveness and its regulation of Wnt signalling. mRNA expression profiles of 32 PA samples were generated by RNA-seq, and proteomic data from 19 samples were obtained by mass spectrometry. Immune-related differentially expressed genes (DEGs) were retrieved from GeneCards. Weighted gene coexpression network analysis identified modules and hub genes linked to invasiveness, while machine learning methods (support vector machine, LASSO, random forest) prioritised key genes. Gene set enrichment analysis (GSEA) assessed pathways associated with candidate gene expression. NR3C1 expression and function were validated by immunohistochemistry, Western blotting and invasion assays. Integration of transcriptomic, proteomic and immune-related datasets yielded 11 overlapping genes, with NR3C1 emerging as the top candidate. NR3C1 was significantly upregulated in NIPAs and demonstrated good discriminatory power by ROC analysis. GSEA associated high NR3C1 expression with Wnt pathway activation. Functional experiments confirmed that NR3C1 overexpression enhances the invasive capacity of PA cells. NR3C1 promotes the invasive phenotype of NIPAs by activating Wnt signalling. These findings suggest NR3C1 as a potential biomarker and therapeutic target for invasive pituitary adenomas.

Humans↗

PubMed2026

GCH1, identified by a ferroptosis-related prognostic model, contributes to progression and drug resistance of esophageal cancer.

OBJECTIVE: Esophageal cancer has a poor prognosis and limited treatment options. Ferroptosis, an iron-dependent cell death pathway, is a promising therapeutic target; however, its significance in esophageal cancer remains largely unexplored. Here, we investigated the prognostic significance of ferroptosis-related genes in esophageal cancer and identified a key functional regulator that may serve as a therapeutic target. METHODS: We analyzed ferroptosis-related gene expression profiles with The Cancer Genome Atlas-Esophageal Carcinoma (TCGA-ESCA) cohort and constructed a prognostic risk model using LASSO Cox regression analysis. Among the genes in this model, GTP cyclohydrolase 1 (GCH1) was selected for functional investigation, based on its established role in antioxidant defense. Subsequently, in vitro experiments were performed to assess the effects of GCH1 knockdown on cell proliferation, migration, clonogenicity, and ferroptosis-related biochemical indicators. The role of GCH1 in antitumor immunity was evaluated through co-culture of esophageal cancer cells with activated T cells, and drug sensitivity was assessed using cytotoxicity assays. RESULTS: A prognostic model consisting of nine ferroptosis-related genes (STC2, TRIB3, HMGB3, CXCL8, GCH1, PARP10, APOE, MTIM, and GPER1) with reliable risk stratification was constructed. The prognostic model could reflect the differences in drug responses and immune cell infiltration. GCH1 knockdown suppressed esophageal cancer cell proliferation, migration, and clonogenicity. Furthermore, GCH1 knockdown increased the intracellular levels of reactive oxygen species, lipid peroxidation, and ferrous iron (Fe2+). Co-culture assays demonstrated that GCH1 knockdown in tumor cells increased the production of granzyme B and interferon-γ by CD8+ T cells. Moreover, GCH1 silencing sensitized esophageal cancer cells to both sorafenib and cisplatin. CONCLUSIONS: This study established a ferroptosis-related prognostic model for esophageal cancer and identified GCH1 as a critical regulator that contributes to esophageal cancer progression and drug resistance. These findings suggest that targeting GCH1 may be a promising strategy to improve drug sensitivity and clinical outcomes in esophageal cancer.

Esophageal cancer↗

PubMed1995

Differential display analysis of gene expression in developing embryos of Xenopus laevis.

Differential display (DD), an arbitrarily primed RT-PCR fingerprinting technique, is a novel approach for the search of differentially expressed transcripts. Using our improved DD protocol, reproducible cDNA fingerprints were successfully obtained from RNAs of Xenopus laevis embryos at six representative stages. Parallel comparison among the fingerprints revealed a number of bands with differential expression patterns. Analysis with clones of three randomly chosen bands confirmed that their expression patterns were faithfully reflected on fingerprints, thereby proving the reliability and validity of the approach. Nucleotide sequencing of these clones revealed that one is identical with a known transcript (cardiac actin), the second is a novel developmentally regulated gene showing no significant homology with those reported previously, and the last is a close but unique relative of XK endo B gene showing somewhat different spatial expression pattern. These results indicated that the DD analysis provides a rapid and reliable way for the identification of novel differentially expressed genes as well as a unique 'scope' for the survey of the changes in overall gene expression profiles occurring in the early embryonic development of Xenopus as well as of other organisms.

Amino Acid Sequence↗

PubMed2025

Higher Expression of HPV16 Derived E7_LI Transcript Observed in Men With HIV and Recurrent Anal Cancer.

Squamous cell carcinoma of the anus (SCCA) or anal cancer (AC) is an understudied cancer with a high occurrence rate in people with HIV (PWH), especially men having sex with men (MSM). Furthermore, AC recurs in approximately one-fourth of patients who undergo standard care with chemoradiation therapy (CRT). Using bulk RNA sequencing data of AC obtained from 12 patients with non-recurrent (NR, N = 9) or recurrent (R, N = 3) cancer, we previously showed upregulated expression of key immune genes in the NR compared to the R group. Although the main causative agent of AC is high-risk human papillomavirus (HPV), association of host and viral RNA transcript expression contributing to AC recurrence has not been extensively studied. The objective of the current study was to determine whether enrichment of specific HPV genotypes and/or HPV gene expression patterns differentiate the two groups and if any specific viral (HPV) and host (human) immune mediators correlate with each other. Using bulk RNA sequencing data and VIRTUS 2, we detected viral RNA reads mapping to seven high-risk and six low-risk HPV types, of which the high-risk HPV16 observed in 83% (10/12) AC tumors (7/9 NR and 3/3 R). Rate of all HPV genomes trended toward a decrease in NR AC isolates and correlation between HPV types was more commonly observed in low-risk ones. Analysis of HPV 16 gene expression profile showed a significantly lower positivity rate for a polycistronic transcript encoding for E7^L1 in the NR group (1/9, NR vs. 3/3, R, p < 0.05). An unbiased correlation analysis of HPV-human transcript expression showed a direct correlation between HPV transcripts and human genes involved in cell growth. The data also identified human transcripts showing an inverse correlation with HPV gene expression. These included genes involved in negative regulation of growth, proliferation, and immune response. Taken together, these data indicate that concurrent analyses of viral and host factors in the same tumor can identify potential new therapeutic targets to ameliorate cancer recurrence post-treatment.

Humans↗

PubMed2014

Molecular heterochrony and the evolution of sociality in bumblebees (Bombus terrestris).

Sibling care is a hallmark of social insects, but its evolution remains challenging to explain at the molecular level. The hypothesis that sibling care evolved from ancestral maternal care in primitively eusocial insects has been elaborated to involve heterochronic changes in gene expression. This elaboration leads to the prediction that workers in these species will show patterns of gene expression more similar to foundress queens, who express maternal care behaviour, than to established queens engaged solely in reproductive behaviour. We tested this idea in bumblebees (Bombus terrestris) using a microarray platform with approximately 4500 genes. Unlike the wasp Polistes metricus, in which support for the above prediction has been obtained, we found that patterns of brain gene expression in foundress and queen bumblebees were more similar to each other than to workers. Comparisons of differentially expressed genes derived from this study and gene lists from microarray studies in Polistes and the honeybee Apis mellifera yielded a shared set of genes involved in the regulation of related social behaviours across independent eusocial lineages. Together, these results suggest that multiple independent evolutions of eusociality in the insects might have involved different evolutionary routes, but nevertheless involved some similarities at the molecular level.

Analysis of Variance↗

PubMed2025

How to analyze and understand the human immune system.

To enhance our understanding of the pathogenesis of diseases, including rheumatic diseases, and to improve disease control, it is essential to attain a thorough understanding of the human immune system, alongside mouse immunology. Historically, the investigation of the human immune system has posed significant challenges due to methodological limitations. Nonetheless, recent advancements in genomic studies of multifactorial diseases have elucidated that numerous risk-associated genetic variants affecting quantitative differences in cell-specific gene expression. In light of these findings, we are currently examining individual genetic variations in both healthy individuals and patients, as well as categorizing cells into distinct subsets in order to construct a comprehensive dataset concerning the human immune system. This is accomplished by combining data on gene expression, factors influencing the expression mechanisms, protein expression, metabolomics, and environmental variables pertinent to immune functionality-such as gut microbiota. These datasets will facilitate the comprehensive characterization of the human immune system. Using these datasets and through the integrative analyses of data related to risk genetic variations and gene expression profiles of each disease and individual, we anticipate uncovering novel insights into the human immune system, the heterogeneity of diseases, immune function mechanisms, and their regulatory strategies that may not be achievable through murine models.

Humans↗

PubMed1993

Perforin and tumor necrosis factor alpha in the pathogenesis of experimental allergic encephalomyelitis: comparison of autoantigen induced and transferred disease in Lewis rats.

A cell-mediated cytotoxic reaction is believed to be involved in inflammatory lesion formation of experimental allergic encephalomyelitis (EAE). We compared EAE diseased animals which had either been immunized with myelin basic protein (MBP) or adoptively received MBP specific T-cell lines in order to study whether the different courses of disease induction are reflected by quantitative or qualitative differences in the expression of genes encoding putative mediators of tissue damage, i.e. TNF alpha, and the pore-forming protein perforin. With the appearance of signs of paralysis, both genes are induced in cells within the CNS lesions, whereas drastically reduced numbers of TNF alpha- and perforin gene-expressing cells are observed during recovery, despite the presence of high numbers of mononuclear cells in the CNS. Marked differences, however, exist in the gene expression profiles: during the phase of most severe clinical signs TNF alpha expressing cells are 2 to 3 times more frequent in transferred than immunized animals. In animals with MBP-induced EAE the number of perforin expressing cells represents only 1.6% of the IL2R gene expressing cells, while this fraction represents 25% in mice which received autoaggressive T cells. Thus, the presence of a high number of activated killer cells may accelerate tissue damage and progression of disease in passive EAE whereas in actively induced EAE activation of regulatory mechanisms induced by polyclonal activation after immunization may prevent generation of large amounts of activated cytotoxic T cells.

Animals↗

PubMed2026

A novel glutamine metabolism-based classification system for characterizing the heterogeneity of hepatocellular carcinoma.

BACKGROUND: Glutamine dependence is a hallmark of tumor cell metabolism, and further molecular classification based on glutamine metabolism in patients with hepatocellular carcinoma (HCC) may provide clinical value. This study thus comprehensively examined the patterns of HCC-specific alterations in glutamine metabolism. METHODS: Consensus clustering analysis was conducted on samples from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset based on glutamine metabolism-related genes, which was validated in the GSE76427, the Liver Cancer-France (LICA-FR) cohort, and the Liver Cancer-Japan (LIRI-JP) cohort from the ICGC. Somatic mutation features were evaluated with the Maftools package in R. The activity of oncogenic pathways was estimated via gene set enrichment analysis (GSEA) or single-sample GSEA (ssGSEA). The tumor microenvironment was analyzed using both the CIBERSORT algorithm (for immune cell infiltration estimation) and the ESTIMATE algorithm (for stromal and immune score calculation). Drug sensitivity and immune checkpoint blockade (ICB) response were also analyzed, for which a classifier was built via least absolute shrinkage and selection operator (LASSO). Immunohistochemistry (IHC) was performed to validate the protein expression levels of key differentially expressed genes (DEGs). Intracellular glutamine content under different glutamine concentrations was measured. The viability of HCC cell lines under varying glutamine concentrations was assessed via Cell Counting Kit-8 (CCK-8) assays. Cell migration and invasion were evaluated through Transwell assays, and protein expression was analyzed via Western blotting. RESULTS: HCC samples were classified into two glutamine metabolism-based clusters, with cluster 1 having a more advanced stage of disease and shorter survival than cluster 2. A higher frequency of genetic mutations and stronger activation of oncogenic pathways was found in cluster 1. There were substantial differences in immune cell infiltration and stromal scores between clusters 1 and 2. Cluster 1 exhibited significantly higher infiltration of immunosuppressive cells and lower stromal scores compared to cluster 2. Cluster 1 had a stronger response to ICB due as indicated by a higher tumor mutation burden (TMB) and T cell-inflamed gene expression profile score, immune checkpoints, and Tumor Immune Dysfunction and Exclusion (TIDE)-predicted data. Moreover, the LASSO classifier accurately differentiated the two clusters. The DEGs between the two clusters were validated in clinical samples. IHC confirmed the differential expression of glutamine metabolism-related genes in HCC samples. CCK-8 assays showed no significant effect of glutamine concentration on cell proliferation. However, Transwell assays revealed that glutamine deprivation (0.2 mM) reduced migration and invasion, while high-glutamine conditions (10 mM) promoted them. Western blotting showed increased expression of metabolism-related proteins under high-glutamine conditions and reduced expression under deprivation. CONCLUSIONS: Altogether, these findings indicate the involvement of glutamine metabolism in HCC and may help inform patient stratification and the formulation of precision therapeutics for this population.

Hepatocellular carcinoma (HCC)↗

PubMed2026

Dysregulated Sheddase Signalling as a Molecular Driver of Plaque Instability Revealed by Integrative Transcriptomics.

Atherosclerosis is a major cause of mortality due to chronic and progressive low-grade inflammation and fibroproliferative remodelling of the intima of arteries. Comprehensive understanding of the interplay between plaque biology and the mechanisms underlying plaque vulnerability and rupture is essential. Here, we aimed to investigate the transcriptomic profiles of stable and unstable atherosclerotic plaques using RNA sequencing data from human carotid atherosclerotic plaque samples based on next-generation knowledge discovery (NGKD) methods. High-throughput RNA-seq data from plaques dissected in stable and unstable regions of four patients were obtained from the Gene Expression Omnibus (GEO) database. GEO RNA-seq Experiments Interactive Navigator (GREIN) software was used to obtain raw gene-level counts and filtered metadata for this dataset. The data were further filtered and normalized using Express analyst to derive differentially expressed genes (DEGs) in unstable plaques compared to stable plaques. The DEGs were further analysed using WebGestalt, STRING DB, preranked gene set enrichment analysis (GSEA), and Ingenuity Pathway Analysis (IPA) software. We identified 4792 DEGs in unstable plaques based on a p-value cutoff of < 0.05. NGKD analysis revealed that the sheddase pathway, collagen degradation, activation of matrix metalloproteinases (MMPs), and extracellular matrix (ECM) degradation ranked among the top five upregulated pathways, whereas the inhibition of MMPs and smooth muscle contraction pathways were identified as the most prominent downregulated pathways in unstable plaques. We found that the sheddase pathway was one of the most significantly upregulated canonical pathways in unstable plaques and this finding opens new avenues for potential therapeutic interventions in patients with atherosclerosis.

Humans↗

PubMed2007

Ovarian cancer biomarkers: a focus on genomic and proteomic findings.

Among the gynaecological malignancies, ovarian cancer is one of the neoplastic forms with the poorest prognosis and with the bad overall and disease-free survival rates than other gynaecological cancers; several studies, analyzing clinical data and pathological features on ovarian cancers, have focused on the identification of both diagnostic and prognostic markers for applications in clinical practice. High-throughput technologies have accelerated the process of biomarker discovery, but their validity should be still demonstrated by extensive researches on sensibility and sensitivity of ovarian cancer novel biomarkers, determining whether gene profiling and proteomics could help differentiate between patients with metastatic ovarian cancer and primary ovarian carcinomas, and their potential impact on management.Therefore, considerable interest lies in identifying molecular prognostic biomarkers and protein indicators to guide treatment decisions and clinical follow up; the current state of knowledge about the potential clinical value of gene expression profiling in ovarian cancer is discussed, focusing on three main areas: distinguishing normal ovarian tissue from ovarian tumors, identifying different subtypes of ovarian cancer and identifying cancer likely to be responsive to therapy.In this elaborate we discuss the use of novel molecules, discovered by proteomics and genomics approaches, as potential protein biomarkers in the management of ovarian cancer, to improve the anticancer therapy for malignant ovarian tumors and to monitor the clinical follow up.

Ovarian cancer↗

PubMed2009

An outlook on ovarian cancer and borderline ovarian tumors: focus on genomic and proteomic findings.

Among the gynaecological malignancies, ovarian cancer is one of the neoplastic forms with the poorest prognosis and with the bad overall and disease-free survival rates than other gynaecological cancers. Ovarian tumors can be classified on the basis of the cells of origin in epithelial, stromal and germ cell tumors. Epithelial ovarian tumors display great histological heterogeneity and can be further subdivided into benign, intermediate or borderline, and invasive tumors. Several studies on ovarian tumors, have focused on the identification of both diagnostic and prognostic markers for applications in clinical practice. High-throughput technologies have accelerated the process of biomolecular study and genomic discovery; unfortunately, validity of these should be still demonstrated by extensive researches on sensibility and sensitivity of ovarian cancer novel biomarkers, determining whether gene profiling and proteomics could help differentiate between patients with metastatic ovarian cancer and primary ovarian carcinomas, and their potential impact on management. Therefore, considerable interest lies in identifying molecular and protein biomarkers and indicators to guide treatment decisions and clinical follow up. In this review, the current state of knowledge about the genoproteomic and potential clinical value of gene expression profiling in ovarian cancer and ovarian borderline tumors is discussed, focusing on three main areas: distinguishing normal ovarian tissue from ovarian cancers and borderline tumors, identifying different genotypes of ovarian tissue and identifying proteins linked to cancer or tumor development. By these targets, authors focus on the use of novel molecules, developed on the proteomics and genomics researches, as potential protein biomarkers in the management of ovarian cancer or borderline tumor, overlooking on current state of the art and on future perspectives of researches.

Ovarian cancer↗

PubMed2026

Genomic, transcriptomic, and molecular predictors of response to neoadjuvant therapy in locally advanced rectal cancer: a narrative review.

Total neoadjuvant therapy (TNT) has emerged as a key treatment paradigm for locally advanced rectal cancer, reducing distant metastasis rates and facilitating organ preservation in selected patients. However, treatment response remains heterogeneous, highlighting the need for biomarkers that can guide treatment selection and optimise outcomes. This narrative review synthesises the current evidence regarding tumour-intrinsic genomic biomarkers associated with response to neoadjuvant therapy, encompassing somatic mutations, germline polymorphisms, gene expression profiles, mismatch repair (MMR) status, protein expression, epigenetic markers, and circulating tumour-derived biomarkers across conventional chemoradiotherapy (CRT) and TNT paradigms. Across the reviewed literature, individual somatic mutations, including KRAS, TP53, and BRAF, demonstrated limited reproducibility as predictive biomarkers, although KRAS mutations were recurrently associated with lower pathological complete response (pCR) rates in CRT-era cohorts. Germline polymorphisms in DNA repair (XRCC1) and folate metabolism (MTHFR) genes showed inconsistent associations with treatment response. In contrast, transcriptomic biomarkers demonstrated greater biological coherence, with proliferative, epithelial-mesenchymal transition, and metabolic signatures frequently associated with treatment resistance, while multi-gene classifiers generally outperformed single-gene markers. Among currently available tumour-intrinsic biomarkers, MMR deficiency was the most consistently reported biomarker associated with reduced response to fluoropyrimidine-based regimens, including TNT, although TNT-specific evidence remains comparatively limited. Dynamic circulating tumour DNA (ctDNA) monitoring, particularly ctDNA clearance during or after therapy, was consistently associated with pathological response and long-term oncologic outcomes across reviewed studies, whereas baseline ctDNA levels showed limited predictive value. Overall, the reviewed literature suggests that biomarker research in rectal cancer has evolved from single-gene analyses towards pathway-level and dynamic biomarkers. The integration of transcriptomic signatures, MMR status, and dynamic ctDNA monitoring may represent a promising strategy for personalising neoadjuvant therapy, improving patient selection for organ-preserving approaches, and enhancing oncologic outcomes in locally advanced rectal cancer. Nevertheless, the evidence base remains heterogeneous, and further prospective validation, assay standardisation, and evaluation within contemporary TNT cohorts are required before these biomarkers can be routinely incorporated into clinical decision-making.

Humans↗

PubMed2026

Synthesis of Padina boergesenii-Derived Zinc Oxide Nanoparticles and their Therapeutic Potential Against Oral Squamous Cell Carcinoma: A Transcriptomic and in Vitro Evaluation.

Cancer remains a major health challenge, with oral squamous cell carcinoma (OSCC) being an high aggressive subtype of head and neck squamous cell carcinoma that lacks effective therapeutic options. Current study integrates the synthesis of zinc oxide nanoparticles (ZnO-NPs) from the marine brown algae Padina boergesenii with the OSCC gene expression profile to evaluate their potential therapeutic effects against OSCC. Herein, the ZnO-NPs from Padina boergesenii were prepared through the green synthesis method. The obtained ZnO-NPs were characterized through spectroscopic methods, the UV spectrophotometer shows maximum absorbance at 372 nm, FT-IR presents Zn-O functional band at 516 cm- 1, HR-TEM confirms average particle size of 55.70 nm and the Zetasizer shows zeta potential of + 12.9 mV, indicating colloidal stability. The cytotoxicity assay with ZnO-NPs against oral cancer cell lines exhibited a reduction in cell viability at IC₅₀ value of 20 µg/mL. Meanwhile, the transcriptome analysis of OSCC highlights that MYC, STAT3, BRCA1, and AKT1 are the OSCC therapeutic targets involved in proliferation, immune evasion, genomic instability, and cancer signalling pathways. Further, qRT-PCR based gene expression analysis demonstrates significant down-regulation of these targets upon ZnO-NPs treatment in KB cell lines. Overall, this study emphasizes the anticancer potential of Padina boergesenii-derived ZnO-NPs that could effectively modulate the therapeutic targets and may benefit the treatment of OSCC cancer.

Cytotoxicity↗

PubMed2025

ATAC-seq for Characterizing Host and Pathogen Genome Accessibility During Virus Infection.

Chromatin regulation provides a mechanism through which cells dynamically and rapidly regulate their gene expression profiles, playing a pivotal role in diverse biological processes and disease states. The Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) is a method that enables genome-wide detection of accessible chromatin regions, providing information on nucleosome positioning and the epigenetic regulation of the chromatin structure. ATAC-seq has been used in various biological contexts, and several reports have demonstrated its application to studying infections with viral or bacterial pathogens. The ability to characterize changes in viral or bacterial genome accessibility during infections provides insights into both pathogen replication and host defense mechanisms. Viral genomes undergo dynamic changes in their structural landscape to facilitate replication and evade host immune responses. Additionally, host cells encode DNA sensors, which are specialized proteins that bind to viral genomes to initiate innate immune responses and sometimes, to suppress viral gene expression. ATAC-seq enables the systematic detection of key structural changes on the viral genome mediated by either viral or host proteins, offering mechanistic insights into virus-host interactions. Here, we describe an ATAC-seq method optimized for studying changes in chromatin accessibility in both host and viral genomes. We have previously applied this method to demonstrate a systematic decrease in the genome accessibility of herpes simplex virus type I (HSV-1) enabled by a host antiviral factor, the interferon-gamma inducible protein 16 (IFI16) during infection of human fibroblasts. This protocol can be adapted to various biological contexts involving the introduction of foreign DNA, making it a valuable tool for a broad range of research endeavors.

Humans↗

PubMed2025

In vivo differentiation of embryonic cells devoid of key reprogramming factors.

Embryonic cell differentiation depends on reprogramming of the oocyte and sperm nucleus into a transient totipotent state. In zebrafish, this coincides with genome activation, which is regulated by the pioneer factors Nanog, Pou5f3, and Sox19b (NPS). Here, we investigate the role of NPS in developmental reprogramming and differentiation by analyzing the fate of NPS mutant cells in a wild-type embryo using single-cell RNA-seq. We find that many cells fail to activate transcription or undergo cell death, while others acquire gene expression profiles that resemble germ cells, neural progenitors, and motoneuron states. These cells achieve intermediate transcriptional states, revealing the essential role of NPS in coordinating nuclear and cytoplasmic reprogramming and preventing the premature activation of lineage-specific differentiation programs. These results demonstrate that most developmental programs require developmental reprogramming by NPS, yet some cells can bypass transient totipotency to achieve intermediate developmental states resembling wild-type states in vivo.

Animals↗

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↗