Colon, rectum and rectal tumor organoids. Effects of calcitriol (active form of Vitamin D) treatment
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA601668 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10902800.fastq.gz | Fastqsanger.gz | |||
| SRR10902801.fastq.gz | Fastqsanger.gz | |||
| SRR10902802.fastq.gz | Fastqsanger.gz | |||
| SRR10902803.fastq.gz | Fastqsanger.gz | |||
| SRR10902804.fastq.gz | Fastqsanger.gz |
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Project description:We have established three-dimensional (3D) organoids from healthy colon and rectum tissue and from tumor tissue of patients with rectal cancer. Global transcriptomic analyses reveal differences in gene expression between these stem cell-derived cultures and distinct response to vitamin D.
2020-09-08 | GSE143782 | GEO
Project description:Glioblastoma is the most common primary brain cancer and is associated with poor survival and high rates of recurrent diseases. The median survival using standard radio-chemotherapy is 15 months and the 5-year survival rate is below 5%. It is hypothesized that treatment resistance, diffuse infiltration of the brain and disease recurrence is, at least in part, due to cancer cells that can obtain a transient, stem-like phenotype. These so-called glioma stem-like cells (GSCs) display pluripotency, express marker proteins associated with stem-cells and can replenish the tumor after treatment. Recently, we have shown that the hormonally active form of vitamin D3, calcitriol (1α,25(OH)2-vitamin D3), is active in a subset of GSCs and reduces traits of stemness. Here, we have employed a set of 8 GSCs that do not respond to calcitriol-treatment (No-responder) and the 8 strongest responders to calcitriol (High-responder) and compared to proteomes after treatment with 50 nM calcitriol for 48h.
2023-11-04 | PXD041634 | Pride
Project description:Effects of calcitriol on expressions of ER stress related genes were evaluated with microarray. Calcitriol, the active form of vitamin D, is known to induce apoptosis in cancer cells and increase intracellular calcium. Increase in cytopalsmic calcicium levels may indicate a decrease in endoplasmic reticulum (ER) calcium levels since ER is the main storage unit for calcium. Decrease in ER calcium levels are known to induce ER stress which can lead to apoptosis. However the effects of calcitriol on ER stress have not been reported before. Here we hypotesized that the cellular effects of calcitriol can be explained by induction of ER stress. We have tested this hypothesis by assessing calcitriol induced transcriptomic alterations with a focus on ER stress related genes.
2015-01-01 | GSE53975 | GEO
Project description:The mechanism of action of vitamin D in prostate cancer (PCa) remains poorly defined, with most mechanisms identified being highly cell type and model specific. One of the underlying factors for these diverse mechanisms may be the use of overly simplistic in vitro model systems to study the complex biology of vitamin D response. Here we use the more complex and in vivo transgenic adenocarcinoma of mouse prostate (TRAMP) model to better determine the mechanism by which vitamin D inhibits PCa growth. In these studies early stage TRAMP mice were treated M-BM-1 20M-NM-<g/kg calcitriol (vitamin D) on a Monday/Wednesday/Friday schedule and tissue was procured 12 and 24 hours post treatment to assess changes in PCa transcriptomes using Affymetrix gene expression arrays. 15 total samples were analyzed. 10 week old TRAMP mice were treated IP M-BM-1 20 ug/kg calcitriol on a Monday/Wednesday/Friday (MWF) schedule, and prostate tissue was procured 12 (N=3, control; N=4, calcitriol) and 24 hours (N=4, control; N=4, calcitriol) post treatment for use in affymetrix studies.
2015-03-02 | E-GEOD-57382 | biostudies-arrayexpress
Project description:Purpose: It has been proposed that vitamin D may play a role in prevention and treatment of cancer while epidemiological studies have linked vitamin D insufficiency to adverse disease outcome in chronic lymphocytic leukemia (CLL). However, the underlying mechanisms have not yet been revealed. In this study, we sought to identify key signaling pathways and molecules that are altered after calcitriol, the biologically active form of vitamin D, supplementation of CLL cells in vitro. Methods: An RNA-Sequencing analysis was performed in primary CLL cells that were treated in vitro with calcitriol. Total RNA was extracted from calcitriol-treated and non-treated CLL cells, while mRNA selection was performed using NEBNext Poly(A) mRNA Magnetic Isolation Module. Library preparation for RNA-Sequencing (RNA-Seq) analysis was conducted with the NEBNext Ultra II Directional RNA Library Prep Kit. The libraries were paired-end sequenced on the NextSeq 500 Illumina platform. Differential expression analysis was performed using DESeq2; genes with log2FC>|1| and P≤0.05 were considered as differentially expressed. Results: Differential expression analysis revealed 85 differentially expressed genes (DEGs) (log2FC≥|1| and p≤0.05), of which 28 (32.9%) were overexpressed in calcitriol-treated cells versus unstimulated CLL cells, thus, contrasting the remaining 57 (67.1%) which showed the opposite pattern. Supervised hierarchical clustering analysis, based on the differentially expressed genes, was performed and revealed distinct gene expression patterns between calcitriol-treated and control CLL cells. Moreover, pathway enrichment analysis revealed that calcitriol-regulated genes are implicated in signaling pathways known to be deregulated in CLL biology. Conclusions: Transcriptome analysis highlighted the possible impact of calcitriol on the regulation of immune signaling pathways relevant to CLL pathophysiology.
2021-01-01 | GSE162427 | GEO
Project description:Cancer cells with a stem-like phenotype are commonly described in glioblastoma, the most common primary adult brain cancer, that are thought to be highly tumorigenic. This phenotype comprimes high self renewal capacity and resistance against chemotherapy and radiation therapy, thereby promoting tumor progression and disease relapse. Here we show for the first time that calcitriol, the hormonally active form of the “sun hormone” vitamin D3, effectively suppresses stemness properties in glioblastoma stem-like cells (GSCs), supporting the hypothesis that cal-citriol sensitizes them to additional chemotherapy. Indeed, a physiologically relevant organotypic brain slice model was used to monitor tumor growth of GSCs and the effectiveness of combined treatment with temozolomide, the current standard-of-care, and calcitriol was proven. These findings indicate that further research on applying calcitriol, a well known and safe drug, as a potential adjuvant therapy for glioblastoma is both justified and necessary.
2021-07-19 | PXD026789 | Pride
Project description:Dicer is a key endoribonuclease of the microRNA biogenetic machinery. Downregulation of Dicer has been associated with aberrant expression of microRNAs and the promotion of tumorigenesis. Calcitriol, the hormonal form of vitamin D3, increases microRNA expression in tumor cells, but the mechanism is not yet understood. Given the essential role of Dicer in microRNAs biogenesis, the purpose of this study was to evaluate whether this gene is a target for calcitriol and to explore the effects of this hormone on microRNA expression. Our findings demonstrate that calcitriol increased Dicer mRNA and protein in SiHa and HeLa cervical cancer cells, which expressed the vitamin D receptor. The inductive effect of calcitriol on Dicer mRNA was not observed in C33-A cells lacking this nuclear receptor. To explore the potential effect of Dicer upregulation by calcitriol on microRNA processing, we performed a microRNA profiling study in SiHa cells treated with calcitriol. The analysis of microRNA expression revealed that this hormone promotes the maturation of a subset of microRNAs with potential regulatory function in cancer pathways. Among these, miR-22 and miR-296-3p have already been associated with tumor-supressive effects. Our results suggest that Dicer upregulation by calcitriol could be associated, at least in part, with an increase in the maturation of a subset of tumor-suppressor microRNAs in cervical cancer cells.
2014-11-30 | GSE61829 | GEO
Project description:Vitamin D deficiency is a major environmental risk factor for the development of multiple sclerosis (MS). The major circulating metabolite of vitamin D (25OHD) is converted to the active form (calcitriol) by the hydroxylase enzyme CYP27B1. In MS lesions the tyrosine kinase MerTK expressed by microglia and macrophages regulates phagocytosis of myelin debris and apoptotic cells that can accumulate and inhibit tissue repair and remyelination. We show that calcitriol downregulates MerTK mRNA and protein expression in primary adult human microglia and monocyte-derived macrophages, thereby inhibiting myelin phagocytosis and apoptotic cell clearance. Proinflammatory myeloid cells express high levels of CYP27B1 compared to homeostatic (TGFb-treated) myeloid cells. Only proinflammatory cells in the presence of TNF-a generate calcitriol from 25OHD, resulting in repression of MerTK expression and function. The selective production of calcitriol in proinflammatory myeloid cells leading to downregulation of MerTK-mediated phagocytosis has the potential to reduce the risk for auto-antigen presentation while retaining the phagocytic ability of homeostatic myeloid cells, thereby contributing to inflammation reduction and enhanced tissue repair.
2020-04-21 | GSE148986 | GEO
Project description:AIM Vitamin D deficiency is associated with risk of several common cancers, including colorectal cancer (CRC). We investigated the effects of vitamin D on in vitro and ex vivo epithelial cell gene expression and assessed dysregulation of pathways involved in anti-tumour effects. METHODS We performed in vitro and ex vivo intervention studies using established CRC cell lines and patient-derived epithelial organoids developed from normal human colonic (resectional colorectal surgery) and rectal mucosa (rectal biopsy). RNA and protein were harvested after 16-24 hours’ calcitriol treatment. Gene expression was assessed by qRT-PCR, microarray and RNA-sequencing, and protein expression by immunoblotting and mass-spectrometry. Gene Ontology enrichment analysis was performed using GOrilla and Gene Set Enrichment Analysis. RESULTS Calcitriol increased the expression of the tumour suppressor gene CDH1 in CRC cell lines (SW480; FC=3.60, 95%CI 2.17-5.03) and patient-derived epithelial cell organoids (n=6, FC=1.64, 95%CI 1.49-1.80), with associated in vitro E-cadherin protein induction. Significant differential expression of a further 6 common genes was observed on microarray analysis of in vitro and ex vivo experiments, including genes with established links to carcinogenesis GADD45, EFTUD1 and KIAA1199. Numerous ontologies relevant to carcinogenesis were enriched (e.g. ‘regulation of Wnt signaling pathway’, ‘regulation of cell death’), with common enriched processes across in vitro and ex vivo cultures including ‘negative regulation of cell proliferation’, ‘regulation of cell migration’ and ‘regulation of cell differentiation’. CONCLUSIONS We report for the first time, common genes and pathways modulated by calcitriol treatment in both in vitro and ex vivo models, with several differentially expressed genes strongly linked to CRC tumourigenesis. Enrichment of biological pathways after calcitriol treatment provides further evidence of anti-tumour effects. These findings support epidemiological data and provide strong rationale for well-designed trials of vitamin D supplementation as a novel CRC chemopreventive and chemotherapeutic agent. see above
2022-06-01 | GSE181644 | GEO
Project description:Controversy surrounds whether vitamin D reduces colorectal cancer (CRC) risk, and/or beneficially impacts on CRC survival. We sought to delineate the transcriptomic in vivo response of human colorectal epithelium to vitamin D supplementation, define inter-subject variability and develop a predictive biomarker of response consistent with anti-tumour effects. Methodology Blood and rectal normal mucosa (NM) were sampled (176 subjects) and correlation sought between circulating vitamin D (25-OHD) level and NM gene expression (HT12 microarray) in the observational study. Oral vitamin D (3200IU/day) supplements were administered to 50 participants in an intervention study. Blood and NM (sigmoidoscopic biopsy) were sampled after 12 weeks. Transcriptomic analysis (HT12 and RNAseq) of post-treatment biopsies assessed enrichment for candidate genes and GO processes prioritised in the observational study. We identified transcriptomic changes in rectum that are consistent with anti-tumour responses. We then sought blood biomarkers predicting this response using receiver-operator curves and calculation of C-statistic. An independent expression dataset (BEST-D trial) was then used to validate candidate blood biomarkers of vitamin D response.
2021-06-22 | GSE157982 | GEO