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Results for “expression atlas”

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At least 73 records · Page 4Linked to original sources

PubMed2001

Quantitative gene expression profiles of human liver-derived cell lines exposed to moderate hypoxia.

AIMS: To obtain better understanding of molecular events following critical oxygen shortage in liver tissue, we performed a large-scale comparison of gene expression profiles in four human liver cell lines, Chang, Hep3B, HuH7, and HepG2. METHODS: We used Atlas cDNA expression arrays from Clontech for initial screening, and quantitative real-time RT-PCR to assess the statistical significance of observed changes. RESULTS: RT-PCR analysis confirmed significantly changed levels of 24 transcripts after 24 hours incubation in 1% O(2). Among the genes most robustly up-regulated were plasminogen activator inhibitor-1 (PAI-1), insulin-like growth factor binding protein-3, and glyceraldehyde-3-phosphate dehydrogenase. Only PAI-1 was concordantly up-regulated in all four cell lines. Conversely, most down-regulated were the stress response genes, including several heat shock proteins, yet only the expression of flap endonuclease-1 was significantly decreased in all cell lines. When comparing individual cell lines, the HepG2 cells displayed a pattern of general down-regulation (83%), followed by Hep3B with 58% of genes down-regulated. In the Chang and HuH7 cells, however, the expression of most genes, 50% and 67%, respectively, remained unchanged. CONCLUSION: These studies provide information that is of importance for improved insight into the responses of not only liver tumor cells but also normal liver tissue in the conditions where physiological oxygenation is severely impaired.

Carcinoma, Hepatocellular↗

PubMed2002

Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing oestrogen receptor alpha.

The purpose of this study was to classify selective oestrogen receptor modulators based on gene expression profiles produced in breast cancer cells expressing either wtERalpha or mutant(351)ERalpha. In total, 54 microarray experiments were carried out by using a commercially available Atlas cDNA Expression Arrays (Clontech), containing 588 cancer-related genes. Nine sets of data were generated for each cell line following 24 h of treatment: expression data were obtained for cells treated with vehicle EtOH (Control); with 10(-9) or 10(-8) M oestradiol; with 10(-6) M 4-hydroxytamoxifen; with 10(-6) M raloxifene; with 10(-6) M idoxifene, with 10(-6) M EM 652, with 10(-6) M GW 7604; with 5 x 10(-5) M resveratrol and with 10(-6) M ICI 182,780. We developed a new algorithm 'Expression Signatures' to classify compounds on the basis of differential gene expression profiles. We created dendrograms for each cell line, in which branches represent relationships between compounds. Additionally, clustering analysis was performed using different subsets of genes to assess the robustness of the analysis. In general, only small differences between gene expression profiles treated with compounds were observed with correlation coefficients ranged from 0.83 to 0.98. This observation may be explained by the use of the same cell context for treatments with compounds that essentially belong to the same class of drugs with oestrogen receptors related mechanisms. The most surprising observation was that ICI 182,780 clustered together with oestrodiol and raloxifene for cells expressing wtERalpha and clustered together with EM 652 for cells expressing mutant(351)ERalpha. These data provide a rationale for a more precise and elaborate study in which custom made oligonucleotide arrays can be used with comprehensive sets of genes known to have consensus and putative oestrogen response elements in their promoter regions.

Breast Neoplasms↗

PubMed2004

Identification of genes differentially expressed in monocyte-derived dendritic cells with 1alpha,25-dihydroxyvitamin D3 using cDNA arrays.

In order to study the molecular mechanism of the inhibitory effect of 1,25-dihydroxyvitamin D(3) on dendritic cells, experiments were performed using Atlas cDNA expression arrays from Clonetech to identify the differentially expressed genes of dendritic cells by 1,25-dihydroxyvitamin D(3). Analysis of cDNA arrays revealed changes in the expression of 9 genes, including those involved in DNA binding and transcription, extracellular cell signaling and communication, intracellular transducers, as well as cell adhesions. The results indicated that a multiple molecular network is involved in the inhibitory role of 1,25-dihydroxyvitamin D(3) on dendritic cells. The Atlas Array technology may facilitate the elucidation of complex pharmacological process of 1,25-dihydroxyvitamin D(3) on dendritic cells.

Calcitriol↗

PubMed2026

Tumor Suppressive Role of Hsa-miR-328-3p in Colon Cancer by Regulating EN2.

BACKGROUND/AIM: Colon cancer is a prevalent and life-threatening malignancy worldwide. Recent studies have focused on how microRNAs (miRNAs) act as post-transcriptional modulators in colon cancer progression. Herein, this study aimed to identify the impact of miRNAs that are decreased in colon cancer and to investigate their regulatory mechanisms. MATERIALS AND METHODS: Differentially expressed miRNAs (DEmiRNAs) and genes (DEGs) were identified through analysis of miRNA sequencing and RNA sequencing data from normal and tumor tissues in The Cancer Genome Atlas (TCGA). Expression levels were validated by quantitative polymerase chain reaction (qPCR) in both tissues and cell lines. Functional effects of miRNAs were evaluated by assessing cell viability, proliferation, migration, and invasion following transfection with miRNA mimics. RESULTS: Analysis of miRNA-seq data from the TCGA database identified hsa-miR-328-3p as a miRNA consistently downregulated across all stages of colon cancer. This downregulation was independently validated in colon cancer patient tissues by qPCR. Functional assays demonstrated that enforced expression of hsa-miR-328-3p significantly reduced cell viability, proliferation, migration, and invasion in colon cancer cell lines, supporting its tumor-suppressive role. To elucidate the molecular mechanism underlying these inhibitory effects, target gene analysis was performed. Engrailed homeobox 2 (EN2) was identified as a potential target of hsa-miR-328-3p, and a dual-luciferase assay confirmed that EN2 is directly regulated by hsa-miR-328-3p. CONCLUSION: Collectively, these findings indicate that hsa-miR-328-3p is frequently downregulated in colon cancer and functions as a tumor suppressor by negatively regulating its target gene, EN2, thereby contributing to colon cancer malignancy. EN2 may serve as a potential diagnostic biomarker for colon cancer, while restoration of hsa-miR-328-3p expression represents a promising therapeutic strategy. Further studies are needed to clarify the precise molecular mechanisms linking the hsa-miR-328-3p/EN2 axis to colon cancer progression.

Humans↗

PubMed2000

Detection of differentially expressed genes in lymphomas using cDNA arrays: identification of clusterin as a new diagnostic marker for anaplastic large-cell lymphomas.

This study reports the first use of gene array technology for the identification of a tumor-specific marker in lymphoid neoplasms. The differential gene expression of 31 hematopoietic cell lines, representing most major lymphoma subgroups of B- and T-cell origin, was assessed by hybridizing labeled complementary DNA to Atlas human expression arrays containing 588 genes. Genes known to be specific for B, T, or myelomonocytic lineages were appropriately identified in the arrays, validating the general utility of this approach. One gene, clusterin, not previously known to be expressed in lymphoid neoplasms, was specifically found in all 4 anaplastic large-cell lymphoma (ALCL) cell lines, but not in any of the 27 remaining tumor lines. Using a monoclonal antibody against clusterin, its differential expression was confirmed by Western blotting and immunohistochemistry. A total of 198 primary lymphomas (representing most major lymphoma subtypes), including 36 cases of systemic ALCL, were surveyed for clusterin expression by immunohistochemistry and Western blotting. All of the 36 ALCL cases marked for clusterin, with most cases showing moderate to strong staining in the majority of neoplastic cells. Clusterin expression was not related to expression of anaplastic lymphoma kinase-1. With 2 exceptions, none of the remaining 162 non-ALCL cases marked with the clusterin antibody, including Hodgkin disease and primary cutaneous ALCL. In reactive lymphoid tissues, only follicular dendritic cells and fibroblastic reticular cells exhibited staining. Clusterin is a highly conserved glycoprotein implicated in intercellular and cell matrix interactions, regulation of the complement system, lipid transport, stress responses, and apoptosis. Although its function in ALCL is unknown, the unique expression of clusterin within this category of lymphoma provides an additional marker for the diagnosis of ALCL. This study illustrates the enormous potential of gene array technologies for diagnostic marker discovery. (Blood. 2000;96:398-404)

Biomarkers, Tumor↗

PubMed2002

Study of gene expression in thyrotropin-stimulated thyroid cells by cDNA expression array: ID3 transcription modulating factor as an early response protein and tumor marker in thyroid carcinomas.

Induction of cell proliferation by mitogen or growth factor stimulation leads to the specific induction or repression of a large number of genes. To identify genes differentially regulated by the cAMP-dependent transduction pathway, which is poorly characterized so far, we used the cDNA expression array technology. Hybridizations of Atlas human cDNA expression arrays with (32)P-labeled cDNA probes derived from control or thyrotropin (TSH)-stimulated dog thyrocytes in primary culture generated expression profiles of hundreds of genes simultaneously. Among the genes that displayed modified expression, we selected the transcription factor ID3, whose expression was increased by a cAMP-dependent stimulus. ID3 overexpression after TSH stimulation was first verified by Northern blotting analysis, and its mRNA regulation was then investigated in response to a variety of agents acting on thyrocyte proliferation and/or differentiation. We show that: (1) ID3 mRNA induction was stronger after stimulation of the cAMP cascade, but was not restricted to this signaling pathway, as phorbol myristate ester (TPA) and insulin also stimulated mRNA accumulation; (2) in contrast, powerful mitogens for thyroid cells, epidermal growth factor and hepatocyte growth factor, did not significantly modify ID3 mRNA levels; (3) ID3 protein levels closely parallelled mRNA levels, as revealed by immunofluorescence experiments showing a nuclear signal regulated by TSH; (4) in papillary thyroid carcinomas, ID3 mRNA was downregulated. Our results suggest that ID3 expression might be more related to the differentiating process induced by TSH than to the proliferative action of this hormone.

Animals↗

PubMed2001

Methylseleninic acid, a potent growth inhibitor of synchronized mouse mammary epithelial tumor cells in vitro.

Selenium compounds have been shown to be effective chemopreventive agents in several animal models and in cultured cells in vitro. It has been proposed that compounds able to generate monomethyl Se have an increased potential to inhibit cell growth. To test this hypothesis, methylseleninic acid (MSeA) and other compounds that could generate methylselenol rapidly were compared with Se compounds that do not generate monomethyl Se, using a well-characterized synchronized TM6 mouse mammary epithelial tumor model in vitro. MSeA at a low micromolar concentration inhibited TM6 growth after 10- to 15-min treatment times. Cells resumed growth after 24 hr but remained sensitive to the fresh addition of monomethyl Se-generators. Dimethyl selenide (DMSe), a putative metabolite of methylselenol, was inactive. Cells treated with 5 microM MSeA were arrested in G1. The effects of 5 microM MSeA on gene expression were evaluated using the Atlas mouse cDNA expression array. A 10-min exposure with MSeA caused a 2- to 3-fold change in the expression of three genes: laminin receptor 1 (decreased), integrin beta (decreased), and Egr-1 (increased). The results provide experimental support for the hypothesis that monomethylated forms of Se are the critical effector molecules in Se-mediated growth inhibition in vitro.

Animals↗

PubMed2003

Molecular fingerprinting of TGFbeta-treated embryonic maxillary mesenchymal cells.

The transforming growth factor-beta (TGF(beta)) family represents a class of signaling molecules that plays a central role in normal embryonic development, specifically in development of the craniofacial region. Members of this family are vital to development of the secondary palate where they regulate maxillary and palate mesenchymal cell proliferation and extracellular matrix synthesis. The function of this growth factor family is particularly critical in that perturbation of either process results in a cleft of the palate. While the cellular and phenotypic effects of TGF(beta) on embryonic craniofacial tissue have been extensively cataloged, the specific genes that function as downstream mediators of TGF(beta) in maxillary/palatal development are poorly defined. Gene expression arrays offer the ability to conduct a rapid, simultaneous assessment of hundreds to thousands of differentially expressed genes in a single study. Inasmuch as the downstream sequelae of TGF(beta) action are only partially defined, a complementary DNA (cDNA) expression array technology (Clontech's Atlas Mouse cDNA Expression Arrays), was utilized to delineate a profile of differentially expressed genes from TGF(beta)-treated primary cultures of murine embryonic maxillary mesenchymal cells. Hybridization of a membrane-based cDNA array (1178 genes) was performed with 32P-labeled cDNA probes synthesized from RNA isolated from either TGF(beta)-treated or vehicle-treated embryonic maxillary mesenchymal cells. Resultant phosphorimages were subject to AtlasImage analysis in order to determine differences in gene expression between control and TGF(beta)-treated maxillary mesenchymal cells. Of the 1178 arrayed genes, 552 (47%) demonstrated detectable levels of expression. Steady state levels of 22 genes were up-regulated, while those of 8 other genes were down-regulated, by a factor of twofold or greater in response to TGF(beta). Affected genes could be grouped into three general functional categories: transcription factors and general DNA-binding proteins; growth factors/signaling molecules; and extracellular matrix and related proteins. The extent of hybridization of each gene was evaluated by comparison with the abundant, constitutively expressed mRNAs: ubiquitin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ornithine decarboxylase (ODC), cytoplasmic beta-actin and 40S ribosomal protein. No detectable changes were observed in the expression levels of these genes in-response to TGF(beta) treatment. Gene expression profiling results were verified by Real-Time quantitative polymerase chain reaction. Utilization of cDNA microarray technology has enabled us to delineate a preliminary transcriptional map of TGF(beta) responsiveness in embryonic maxillary mesenchymal cells. The profile of differentially expressed genes offers revealing insights into potential molecular regulatory mechanisms employed by TGF(beta) in orchestrating craniofacial ontogeny.

Animals↗

PubMedDate not supplied

Analysis of intestinal adaptation gene expression by cDNA expression arrays.

BACKGROUND: As a tool for determining gene expression on a genomic scale, cDNA microarrays are a promising new technology that can be applied to the study of complex physiologic processes. The objective of this study was to characterize the expression of individual genes and patterns of gene expression that might provide insight into the mechanism of intestinal adaptation after massive small bowel resection. METHODS: Male ICR mice underwent a 50% proximal small bowel resection (SBR) or sham operation. After 3 days, the remnant ileum was harvested, weighed, and RNA extracted. Changes in gene expression were detected utilizing Clontech Atlas mouse cDNA expression arrays. Some of these changes were confirmed by reverse transcriptase-polymerase chain reactions (RT-PCR) and Northern blots. RESULTS: Analysis of these cDNA arrays revealed changes in the expression of multiple genes, including those involved in cell cycle regulation, apoptosis, DNA synthesis, and transcriptional regulation. The patterns of expression were consistent with the increased cell proliferation and apoptosis observed during intestinal adaptation. A large number of genes not previously associated with intestinal adaptation were identified. CONCLUSIONS: This technology may facilitate the elucidation of the intricate cellular mechanisms underlying intestinal adaptation.

Adaptation, Biological↗

PubMed2004

Formalization of mouse embryo anatomy.

MOTIVATION: The Edinburgh Mouse Atlas and Gene Expression Database project has developed a digital atlas of mouse development to provide a spatio-temporal framework for spatially mapped data such as in situ gene expression and cell lineage. As part of this database, a mouse embryo anatomy ontology has been created. A formalization of this anatomy is required to document its precise semantics and how it is used in the context of the Mouse Atlas. RESULTS: The paper describes the existing anatomy ontology and formalizes aspects of it using a predicate logic based approach. It therefore provides a guide for users of the current version of the ontology, as well as the basis for a description of the anatomy using an ontology language, such as OWL, thus enabling future work on reasoning about the Mouse Atlas in the context of an intelligent gene expression bioinformatics workflow system. The logic has been implemented in a Prolog prototype. AVAILABILITY: The Mouse Atlas is available on-line at http://genex.hgu.mrc.ac.uk

Algorithms↗

PubMed1998

Inhibition of alanyl aminopeptidase induces MAP-kinase p42/ERK2 in the human T cell line KARPAS-299.

Inhibition of alanyl aminopeptidase (EC 3.4.11.2, aminopeptidase N, CD13) expression, or activity compromise cell proliferation in a number of cell systems [1, 2, 3, 4, 5, 6]. The underlying mechanisms and the molecular components involved have not been identified as yet. In this study we show that inhibition of alanyl aminopeptidase enzymatic activity decreases the proliferation rate of the CD13-positive T cell line Karpas-299. By using the ATLAS cDNA expression array (Clontech) we identified the p42/ERK2 MAP kinase as one downstream target of probestin, a potent inhibitor of alanyl aminopeptidase. Probestin and another specific aminopeptidase inhibitor, actinonin, in addition to their capability of inducing erk-2 mRNA levels, significantly increase p42 phosphorylation state. This is the first report on signal transduction components possibly mediating the growth-modulatory effects of alanyl aminopeptidase inhibitors.

CD13 Antigens↗

PubMed2000

Discovery of new inducible genes in in vitro decidualized human endometrial stromal cells using microarray technology.

A prerequisite for implantation in humans is differentiation (decidualization) of stromal cells in the endometrium, believed to be stimulated by progesterone (P) and/or cAMP. In the current study, advances in microarray technology have allowed us to investigate genes differentially expressed in human endometrial stromal cells decidualized in vitro in response to P or cAMP, compared to nondecidualized cells. Endometrial stromal cells were isolated from endometrial biopsy tissue and cultured without steroid hormones, with 1 microM P (after E2 priming), or 1 mM 8-bromo-cAMP. Total RNA was isolated and reverse transcribed to synthesize 32P-labeled cDNA probes using primers corresponding to genes represented on the Clontech Human Atlas cDNA Expression Array. After hybridization, signals were quantified by phosphor imaging densitometry and were normalized to GAPDH and ubiquitin. Of the 588 genes screened, marked upregulation was observed of cytokines, growth factors, nuclear transcription factors, members of the cyclin family, and mediators of the cAMP signal transduction pathway. Additional mRNAs expressed unexpectedly and regulated by P and cAMP, include the insulin receptor, some neurotransmitter receptors, neuromodulators, the FSH receptor, inhibin/activin betaA subunit, inhibin alpha, and TNF-related apoptosis-inducing ligand (TRAIL). Expression of previously unrecognized genes regulated in decidualized human endometrial stromal cells suggests mechanisms not yet appreciated in the endometrium during decidualization. In addition, marked upregulation of cytokines, chemokines, growth factors, apoptosis modulators, and their receptors in decidualized stromal cells supports a major role for paracrine interactions between the stroma and other endogenous and transient cell populations within the endometrium and during early pregnancy.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2002

Alteration of gene expression profiles in skeletal muscle of rats exposed to microgravity during a spaceflight.

To clarify the mechanism of skeletal muscle wasting during spaceflights, we investigated whether intramuscular gene expression profiles are affected, by using DNA microarray methods. Male rats sent on the 17-day NASA STS-90 Neurolab spaceflight were sacrificed 24 hours after return to earth (MG group). Ground control rats were maintained for 17 days in flight-simulated cages (CS group). Spaceflight induced a 19% and 23% loss of tibialis anterior and gastrocnemius muscle mass, respectively, as compared to ground controls. Muscle RNA was analyzed by the Clontech Atlas DNA expression array in four rats, with two MG/ CS pairs for the tibialis anterior, and one pair for the gastrocnemius. Alterations in gene expression were verified for selected genes by reverse-transcription PCR. In both muscles of MG rats, mRNAs for 12 genes were up-regulated by over 2-fold, and 38 were down-regulated compared to controls. There was inhibition of genes for cell proliferation and growth factor cascades, including cell cycle genes and signal transduction proteins, such as p21 Cip1, retinoblastoma (Rb), cyclins G1/S, -E and -D3, MAP kinase 3, MAD3, and ras related protein RAB2. These data indicate that following exposure to microgravity, there is downregulation of genes involved in regulation of muscle satellite cell replication.

Animals↗

PubMed2004

Time- and dose-dependent analysis of gene expression using microarrays in sulfur mustard-exposed mice.

The chemical warfare agent sulfur mustard (SM) produces blister formation with a severe inflammatory reaction in skin of exposed individuals. The development of efficacious countermeasures against SM vesication requires an understanding of the cellular and molecular mechanism of SM-induced tissue injury. This study examined SM-induced alterations in gene expression using Atlas Mouse 5K DNA microarrays (5002 genes) to identify transcriptional events associated with SM skin injury. Mice (N=3) were exposed topically to SM (0.04, 0.08, and 0.16 mg; 48.8, 97.5, and 195 mM) on the inner surface of the right ear and skin tissues were harvested at 1.5, 3, 6, and 12 h. Genes were selected based on the three mice in the same dose group demonstrating a > or =2-fold increase or decrease in gene expression for the SM-exposed tissue when compared to the dichloromethane vehicle control ear at all three doses and four time points. At the 0.04 mg SM dose, the genes observed were primarily involved in inflammation, apoptosis, and cell cycle regulation. Exposure to 0.08 mg SM increased the expression of genes related to inflammation and cell cycle regulation. Exposure to 0.16 mg SM led to a total of six genes that were changed at all observed time periods; however, these genes do not appear to be directly influential in biological mechanisms such as inflammation, apoptosis, and cell cycle regulation as was observed at the lower SM doses of 0.04 and 0.08 mg. These functional categories have been observed in previous studies utilizing both in vivo and in vitro model systems of SM-induced dermal injury, suggesting that molecular mechanisms associated with inflammation, apoptosis, and cell cycle regulation may be appropriate targets for developing prophylactic/therapeutic treatments for SM skin injury.

Animals↗

PubMed2000

The use of large-scale cDNA analysis to profile differential gene expression in KYSE 410 human esophageal cancer cells after irradiation.

Atlas Human cDNA Expression Array, which includes 588 genes divided into functional classes, was used to study gene expression profiles in KYSE 410 human esophageal cancer cells irradiated in doses of 6 and 18 Gy. Considerable changes in the expression of a number of genes was found, including down-regulation of 3 cell cycle regulators and up-regulation of an apoptosis-related gene. Comparison of the expression profiles and identification of genes were performed with Atlas Vision 3.0 software.

Esophageal Neoplasms↗

PubMed1997

Atlas of the neurons that express mRNA for the long form of the prolactin receptor in the forebrain of the female rat.

Prolactin has a variety of important physiological effects on peripheral tissue and on the brain. The behavioral effects of prolactin include the induction of maternal behavior and increased food intake. Prolactin acts via its cognate receptors which have two forms, a short and a long form. The long form of the receptor is predominant in the preoptic area-hypothalamus and is positioned to support maternal behavior since this form is regulated across pregnancy and lactation (Nagano and Kelly [1994] J. Biol. Chem. 269:13337-13345; Sugiyama et al. [1994] J. Endocrinol. 141:325-333). By using in situ hybridization with [33P] labelled cRNA probe specific for the long form of the receptor mRNA(L-PRL mRNA) we have mapped, in brains from 2- and 21-day-old pregnant females, the neuroanatomical distribution of neurons expressing the long form of the receptor. Many neurons with high expression of L-PRL mRNA were located in the anteroventral periventricular nucleus, the medial preoptic area (MPO), specific subdivisions of the paraventricular and supraoptic nuclei, and in the arcuate and ventromedial nuclei. Labelled neurons were also found in limbic system structures such as the bed nucleus of stria terminalis (BST) and the medial nucleus of the amygdala, in a few thalamic nuclei, and in the central gray. All cells throughout the choroid plexus expressed high levels of L-PRL mRNA. The levels of L-PRL mRNA were higher in females on day 21 of pregnancy in the MPO and in the choroid plexus, than in females on day 2 of pregnancy; levels in the ventromedial nucleus of the hypothalamus (VMH) were unchanged across pregnancy. The neuroanatomical distribution of neurons expressing L-PRL mRNA may have special relevance for the mediation of maternal behavior, lactation, sexual behavior, and feeding.

Animals↗

PubMed1997

The mouse atlas and graphical gene-expression database

The large amounts of gene-expression data on mouse development are now too extensive to be stored in any format other than that of a database. Furthermore, as this data is intrinsically graphical and as, in the early developmental stages at least, its boundaries do not map directly to those of anatomical tissues, the natural way to store it is in graphical format. We are therefore constructing a database able to handle such graphical gene-expression data by mapping it onto 3-D reconstructions of mouse embryos whose tissues have been delineated. This article reviews the progress that has been made in this project and describes its two major components, CD-ROMs of the 3-D reconstructions to be held on the user's computer and a gene-expression database that will be maintained at a host site, the two being linked over the internet by a complex Java-based interface for submitting data and querying the database.Copyright 1997 Academic Press Limited Copyright 1997Academic Press Limited

Journal Article↗

PubMed2026

SYT8 Drives Colorectal Cancer Progression and Immune Evasion via the SETD1A-H3K4me3 Axis.

By integrating transcriptomic data from The Cancer Genome Atlas, Gene Expression Omnibus, and a self-established colorectal cancer (CRC) cohort, it was identified that synaptotagmin 8 (SYT8) is significantly up-regulated in tumors and is predictive of poor prognosis. Single-cell RNA sequencing, immunohistochemistry, and immunofluorescence experiments demonstrate that SYT8 expression is largely confined to tumor cells, predominantly in the nucleus. Functional assays reveal that depletion of SYT8 impairs, whereas its overexpression enhances, CRC cell proliferation and invasion. Transcriptomic profiling indicates an enrichment of cell cycle and epithelial-mesenchymal transition signatures. Mechanistically, co-immunoprecipitation/mass spectrometry identifies SET domain containing 1A (SETD1A) as a direct SYT8-interacting partner. The SYT8-SETD1A axis forms a positive-feedback loop that increases histone H3 lysine 4 trimethylation (H3K4me3) levels and drives the transcription of protumorigenic genes. Immune profiling further indicates that high SYT8 expression correlates with increased regulatory T-cell infiltration, suggesting an immunosuppressive microenvironment and potential resistance to immunotherapy. Collectively, SYT8 promotes CRC progression through the SETD1A/H3K4me3-mediated activation of the cell cycle, induction of epithelial-mesenchymal transition, and remodeling of the immune microenvironment. Therefore, SYT8 is established as a prognostic biomarker and serves as a therapeutic target in colorectal cancer.

Humans↗