Gene expression changes in triple-negative breast cancer by glucose restriction and cariporide treatment
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE274176 | GEO | 2024/11/30
REPOSITORIES: GEO
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Project description:We compare global gene expression changes in the Min6 cell line in response to altered glucose flux and pharmacological manipulation of the O-GlcNAc postranslational protein modification. Min6 cells were treated for 1hr in the following conditions: Low glucose (LG), high glucose (HG) and LG+GlcNAcstatin (LG+GNS). After treatment, total RNA was extracted and used for sequencing.
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Project description:Application of autologous adipose-derived stem cells (ASC) for diabetic chronic wounds has become an emerging treatment option. However, ASCs from diabetic individuals showed impaired cell function and suboptimal wound healing effects. We proposed that adopting a low glucose level in the culture medium for diabetic ASCs may restore their pro-healing capabilities. ASCs from diabetic humans and mice were retrieved and cultured in high-glucose (HG, 4.5 g/L) or low-glucose (LG, 1.0 g/L) conditions. Cell characteristics and functions were investigated in vitro. Moreover, we applied diabetic murine ASCs cultured in HG or LG condition to a wound healing model in diabetic mice to compare their healing capabilities in vivo. Human ASCs exhibited decreased cell proliferation and migration with enhanced senescence when cultured in HG condition in vitro. Similar findings were noted in ASCs derived from diabetic mice. The inferior cellular functions could be partially recovered when they were cultured in LG condition. In the animal study, wounds healed faster when treated with HG or LG-cultured diabetic ASCs relative to the control group. Moreover, higher collagen density, more angiogenesis and cellular retention of applied ASCs were found in wound tissues treated with diabetic ASCs cultured in LG condition. In line with the literature, our study showed that a diabetic milieu exerts an adverse effect on ASCs. Adopting LG culture condition is a simple and effective approach to enhance the wound healing capabilities of diabetic ASCs, which is valuable for the clinical application of autologous ASCs from diabetic patients.
2023-08-23 | GSE229387 | GEO
Project description:To comprehensively identify the glucose-regulated lncRNAs, we have employed ArraryStar LncRNA Microarry discovery platform to detect lncRNA expression in glucose-starved and glucose-stimulated triple-negative breast cancer cells. Differentially expressed LncRNAs with statistical significance were identified through Volcano Plot filtering between two groups.
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Project description:Transcriptome of human retinal endothelial cells (hRECs) treated with low glucose (LG), high glucose (HG) or high glucose with 4 uM TTR (HG+TTR) were conducted. Differentially expressed lncRNAs, mRNAs and TTR related lncRNAs and mRNA were acquired for further analysis. Functional annotation and enrichment including KEGG pathway, GO and GSEA were applied to analyze TTR regulated pathway and process. WGCNA analysis was implemented to obtain hub modules and genes. LncRNA-mRNA regulatory network were constructed based on cis, trans and ceRNA acting mode.
2018-07-18 | GSE117238 | GEO
Project description:Aims/hypothesis: Recurrent hypoglycaemia (RH) is a major side-effect of intensive insulin therapy for people with diabetes. Changes in hypoglycaemia sensing by the brain contribute to the development of impaired counterregulatory responses to and awareness of hypoglycaemia. Little is known about the intrinsic changes in human astrocytes in response to acute and recurrent low glucose (RLG) exposure. Methods: Human primary astrocytes (HPA) were exposed to zero, one, three or four bouts of low glucose (0.1 mmol/l) for three hours per day for four days to mimic RH. On the fourth day, DNA and RNA were collected. Differential gene expression and ontology analyses were performed using DESeq2 and GOseq respectively. DNA methylation was assessed using the Infinium MethylationEPIC BeadChip platform. Results: 24 differentially expressed genes (DEGs) were detected (after correction for multiple comparisons). One bout of low glucose exposure had the largest effect on gene expression. Pathway analyses revealed that endoplasmic-reticulum (ER) stress-related genes such as HSPA5, XBP1, and MANF, involved in the unfolded protein response (UPR), were all significantly increased following LG exposure, which was diminished following RLG. There was little correlation between differentially methylated positions and changes in gene expression yet the number of bouts of LG exposure produced distinct methylation signatures. Conclusions/interpretation: These data suggest that exposure of human astrocytes to transient LG triggers activation of genes involved in the UPR linked to endoplasmic reticulum (ER) stress. Following RLG, the activation of UPR related genes was diminished, suggesting attenuated ER stress. This may be mediated by metabolic adaptations to better preserve intracellular and/or ER ATP levels, but this requires further investigation.
2021-02-17 | GSE166845 | GEO
Project description:Aims/hypothesis: Recurrent hypoglycaemia (RH) is a major side-effect of intensive insulin therapy for people with diabetes. Changes in hypoglycaemia sensing by the brain contribute to the development of impaired counterregulatory responses to and awareness of hypoglycaemia. Little is known about the intrinsic changes in human astrocytes in response to acute and recurrent low glucose (RLG) exposure. Methods: Human primary astrocytes (HPA) were exposed to zero, one, three or four bouts of low glucose (0.1 mmol/l) for three hours per day for four days to mimic RH. On the fourth day, DNA and RNA were collected. Differential gene expression and ontology analyses were performed using DESeq2 and GOseq respectively. DNA methylation was assessed using the Infinium MethylationEPIC BeadChip platform. Results: 24 differentially expressed genes (DEGs) were detected (after correction for multiple comparisons). One bout of low glucose exposure had the largest effect on gene expression. Pathway analyses revealed that endoplasmic-reticulum (ER) stress-related genes such as HSPA5, XBP1, and MANF, involved in the unfolded protein response (UPR), were all significantly increased following LG exposure, which was diminished following RLG. There was little correlation between differentially methylated positions and changes in gene expression yet the number of bouts of LG exposure produced distinct methylation signatures. Conclusions/interpretation: These data suggest that exposure of human astrocytes to transient LG triggers activation of genes involved in the UPR linked to endoplasmic reticulum (ER) stress. Following RLG, the activation of UPR related genes was diminished, suggesting attenuated ER stress. This may be mediated by metabolic adaptations to better preserve intracellular and/or ER ATP levels, but this requires further investigation.
2021-02-17 | GSE166847 | GEO
Project description:Gene expression changes in triple-negative breast cancer by glucose restriction and cariporide treatment
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Project description:Obesity is associated with insulin resistance and type 2 diabetes, implying a role for adipose tissue in the etiology of these disorders. We used cDNA microarrays to obtain expression profiles of adipocyte by the treatment of insulin and anti-diabetic drug rosiglitazone at both high and low glucose level. Mouse 3T3-L1 mature adipocytes were treated 2 days 1) with or without 1 µM insulin at low and high glucose level, 2) with or without 0.5 μM rosiglitazone at low and high glucose and insulin level. 1) The comparison between the insulin and non-insulin treatment at the same glucose level showed minor changes in the transcriptome. The expressions of some processing enzymes for extracellular matrix components were regulated by insulin. 2) Transcriptome data indicates that an altered energy metabolism is induced by rosiglitazone in mature adipocytes. In addition, rosiglitazone represses adipokine expression, except adiponectin and ApoE. Moreover, transcriptome changes indicate that a general repression of secreted protein encoding genes occurs. Keywords: homone and drug response
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Project description:Metabolic diseases, including type 2 diabetes and obesity are relevant negative prognostic factor in patients with breast cancer (BC). We have investigated the mechanisms through which elevated glucose levels affect tamoxifen sensitivity of estrogen receptor positive (ER+) BC cells. We found that MCF7 BC cell sensitivity to tamoxifen was 2-fold reduced in 25mM glucose (HG), a concentration mimicking hyperglycaemia, compared to 5.5 mM glucose (LG), resembling normal fasting glucose levels in humans. Shifting MCF7 cells from HG to LG ameliorated their responsiveness to tamoxifen. RNA-Sequencing revealed that glucose modified the transcriptome of MCF7 cells. In particular, cell cycle-related genes were affected by glucose. Combining gene specific knockdown and treatment with human recombinant proteins, we identified the Connective Tissue Growth Factor (CTGF) as glucose-induced factor able to reduce MCF7 cell sensitivity to tamoxifen. Moreover, we found that both CTGF expression levels and tamoxifen responsiveness were enhanced co-culturing MCF7 cells with human adipocytes through an Interleukin-8 (IL8)-mediated mechanism. Indeed, IL8 inhibition reduced CTGF levels and rescued tamoxifen sensitivity in MCF7 cells. Interestingly, CTGF immuno-detection in bioptic specimens obtained from women with ER+ BC correlated with distant metastases (P-value = 0.000), hormone therapy resistance (P-value = 0.000), reduced overall (P-value = 0.051) and disease free survival (P-value = 0.000). Thus, glucose affects tamoxifen responsiveness directly modulating CTGF in BC cells, and indirectly promoting the adipocytes’ release of IL8. Both CTGF and IL8 may represent potential targets in novel therapeutic strategies to increase tamoxifen sensitivity.
2017-07-01 | GSE97647 | GEO
Project description:Tissue samples were cut into 8-µm frozen sections and then microdissected to obtain ~4,000 breast cancer epithelial cells using a P.A.L.M. MicroBeam system (Carl Zeiss MicroImaging, GmbH, Munich, Germany). Proteins were extracted from microdissected cells, followed by denaturation, reduction and alkylation. Protein samples were digested at 37oC for 4 h using MS-grade trypsin (Promega, Madison, WI, USA) at a 1:4 (enzyme:protein) ratio, and then acidified for further analysis. Global proteomic profiles of 126 TNBC samples were recorded on a nanoscale LC hyphenated LTQ-Orbitrap-XL MS system (ThermoElectron, Bremen, Germany). Peptide mixtures were separated on the nLC system (Ultimate 3000, Dionex, Amsterdam, The Netherlands) with a 3-h binary gradient (mobile phase A: H2O, mobile phase B: ACN) in a 3-μm C18 silica packed 50-cm capillary column with 75-μm inner-diameter. Mass spectra were acquired over a mass-to-charge ratio (m/z) range of 400–1,800 at a resolving power of 30,000 at 400 m/z. The top five most intensive parent ions from the full scan were isolated and fragmented by collisional activated dissociation in the linear ion trap. Dynamic exclusion was used to increase number of parent ions selected for fragmentation. MaxQuant search used Carbamidomethylation as a fixed modification for cysteine-containing peptides, and oxidation of methionine and N-terminal acetylation as variable modification.
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