Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1137560 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29888582_1.fastq.gz | Fastqsanger.gz | |||
| SRR29888582_2.fastq.gz | Fastqsanger.gz | |||
| SRR29888583_1.fastq.gz | Fastqsanger.gz | |||
| SRR29888583_2.fastq.gz | Fastqsanger.gz | |||
| SRR29888584_1.fastq.gz | Fastqsanger.gz |
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Project description:Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. TNBC exists widely reprogrammed lipid metabolism, and its metabolic-associated proteins and oncometabolites are promising as potential therapeutic targets. Dandelion (Taraxacum mongolicum) is a classical herbal medicine used to treat breast diseases based on traditional Chinese medicine theory and was reported to have antitumor effects and lipid regulatory capacities. Our previous study showed that dandelion extract was effective against TNBC. However, whether dandelion extract could regulate the lipid metabolisms of TNBC and exert its antitumor effects via interfering with lipids metabolism remained unclear. In this study, an integrated approach combined with network pharmacology and multi-omics techniques (including proteomics, metabolomics, and lipidomics) was performed to investigate the potential regulatory mechanisms of dandelion extract against TNBC. We first determined the antitumor effects of dandelion extract in vitro and in vivo. Then, network pharmacology analysis speculated the antitumor effects involving various metabolic processes, and the multi-omics results of the cells, tumor tissues, and plasma revealed the changes in the metabolites and metabolic-associated proteins after dandelion extract treatment. The alteration of glycerophospholipids and unsaturated fatty acids were the most remarkable types of metabolites. Therefore, the metabolism of glycerophospholipids and unsaturated fatty acids, and their corresponding proteins CHKA and FADS2, were considered the primary regulatory pathways and biomarkers of dandelion extract against TNBC. Subsequently, experimental validation showed that dandelion extract decreased CHKA expression, leading to the inhibition of the PI3K/AKT pathway and its downstream targets, SREBP and FADS2. Finally, the molecular docking simulation suggested that picrasinoside F and luteolin in dandelion extract had the most highly binding scores with CHKA, indicating they may be the potential CHKA inhibitors to regulate glycerophospholipids metabolisms of TNBC. In conclusion, we confirmed the antitumor effects of dandelion extract against TNBC cells in vitro and demonstrated that dandelion extract could interfere with glycerophospholipids and unsaturated fatty acids metabolism via downregulating the CHKA expression and thus inhibiting PI3K/AKT/SREBP/FADS2 axis.
2022-10-14 | PXD035797 | Pride
Project description:To identify novel molecular targets for triple negative breast cancer (TNBC), we have employed whole genome microarray expression profiling. We purified 30 surgically resected breast cancer tissue diagnosed triple negative by means of immunohistochemical staining and 13 normal mammary ductal cells with lasermicrobeam microdissection system (PALM MicroBeam, Carl Zeiss MicroImaging Co., Ltd), performed whole human genome microarray, and compared gene expression levels of TNBC, normal mammary ductal cells, and normal vital organs to develop molecular targets with a minimum risk. Gene expression levels of 30 TNBC, 13 normal mammary ductal cells, and 4 normal vital tissues were evaluated. to clarify the molecular mechanism involved in TNBC, we analyzed gene expression profiles of 30 TNBC as well as 13 normal epithelial ductal cells purified by laser microbeam microdissection, and identified 301 transcripts that were significantly up-regulated and 321 transcripts that were significantly down-regulated in TNBC. In addition, gene-expression profiles analysis of normal human vital organs including heart, lung, liver, and kidney allowed us to identify 90 cancer-specific genes involved in breast carcinogenesis such as NEK2, PBK, DTL, MELK and GPSM2. Among them, we focused on cell cycle regulators, asp (abnormal spindle) homolog, microcephaly associated (Drosophila) (ASPM) and centromere protein K (CENPK) as novel therapeutic targets for TNBC.
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Project description:The shift on energetic demands of proliferating cells during tumorigenesis requires an intense crosstalk between cell cycle and metabolism. Beyond their role in cell proliferation, cell cycle regulators also modulate intracellular metabolism of normal tissues. Using both genetic and pharmacological approaches, we aimed to determine the metabolic role of CDK4 in TNBC cells. Unexpectedly, deletion of CDK4 only slightly reduces cell proliferation of triple negative breast cancer (TNBC) cell line and allows in vivo tumor formation. Furthermore, pro-apoptotic stimuli fail to induce proper cell death in CDK4-silenced, depleted or long-term CDK4/6 inhibitors-treated TNBC cells, with dampened mitochondrial calcium uptake. In the first mass spectrometry-based experiment linked to this project, we explored the proteome and phosphoproteome of WT vs CDK4 KO in triple negative breast cancer cells (MDA-MB-231).
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Project description:Triple-negative breast cancer (TNBC) is malignant cancer with a high risk of recurrence. To date, the underlying 3D chromatin organizations of TNBC have remained unclear. Here, using in situ Hi-C, we characterized the 3D chromatin organizations in cells representing five distinct subtypes of breast cancer (including TNBC) and TNBC tissues, compared to normal cells/tissues. We found that the global and local 3D architectures are severely disrupted in TNBC cells. Importantly, we detected CTCF-dependent TNBC-susceptible loss/gain of 3D chromatin organizations and found that these changes were strongly associated with perturbed chromatin accessibility and transcriptional dysregulations. Although some discrepancies exist between TNBC cell lines and tissues, we observed that perturbed local 3D architectures found in TNBC cells are partially conserved in TNBC tissues. Furthermore, we discovered distinct tissue-specific chromatin loops by comparing normal and TNBC tissues. Collectively, our findings provide important features of 3D chromatin organization in TNBC.
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Project description:Triple-negative breast cancer (TNBC) is malignant cancer with a high risk of recurrence. To date, the underlying 3D chromatin organizations of TNBC have remained unclear. Here, using in situ Hi-C, we characterized the 3D chromatin organizations in cells representing five distinct subtypes of breast cancer (including TNBC) and TNBC tissues, compared to normal cells/tissues. We found that the global and local 3D architectures are severely disrupted in TNBC cells. Importantly, we detected CTCF-dependent TNBC-susceptible loss/gain of 3D chromatin organizations and found that these changes were strongly associated with perturbed chromatin accessibility and transcriptional dysregulations. Although some discrepancies exist between TNBC cell lines and tissues, we observed that perturbed local 3D architectures found in TNBC cells are partially conserved in TNBC tissues. Furthermore, we discovered distinct tissue-specific chromatin loops by comparing normal and TNBC tissues. Collectively, our findings provide important features of 3D chromatin organization in TNBC.
2022-05-06 | GSE167151 | GEO
Project description:Triple-negative breast cancer (TNBC) is malignant cancer with a high risk of recurrence. To date, the underlying 3D chromatin organizations of TNBC have remained unclear. Here, using in situ Hi-C, we characterized the 3D chromatin organizations in cells representing five distinct subtypes of breast cancer (including TNBC) and TNBC tissues, compared to normal cells/tissues. We found that the global and local 3D architectures are severely disrupted in TNBC cells. Importantly, we detected CTCF-dependent TNBC-susceptible loss/gain of 3D chromatin organizations and found that these changes were strongly associated with perturbed chromatin accessibility and transcriptional dysregulations. Although some discrepancies exist between TNBC cell lines and tissues, we observed that perturbed local 3D architectures found in TNBC cells are partially conserved in TNBC tissues. Furthermore, we discovered distinct tissue-specific chromatin loops by comparing normal and TNBC tissues. Collectively, our findings provide important features of 3D chromatin organization in TNBC.
2022-05-06 | GSE167150 | GEO
Project description:The shift on energetic demands of proliferating cells during tumorigenesis requires an intense crosstalk between cell cycle and metabolism. Beyond their role in cell proliferation, cell cycle regulators also modulate intracellular metabolism of normal tissues. Using both genetic and pharmacological approaches, we aimed to determine the metabolic role of CDK4 in TNBC cells. Unexpectedly, deletion of CDK4 only slightly reduces cell proliferation of triple negative breast cancer (TNBC) cell line and allows in vivo tumor formation. Furthermore, pro-apoptotic stimuli fail to induce proper cell death in CDK4-silenced, depleted or long-term CDK4/6 inhibitors-treated TNBC cells, with dampened mitochondrial calcium uptake. In the third mass spectrometry-based experiment linked to this project, we assayed the proteome and phosphoproteome of purified mitochondria-ER junctions in WT and Cdk4 KO triple negative breast cancer cells (MDA-MB-231).
2024-11-26 | PXD046327 | Pride
Project description:Targeted treatment for triple-negative breast cancer (TNBC) remains an elusive clinical challenge. Cyclin-dependent kinase 9 (CDK9) is a transcriptional regulator shown to promote growth of multiple cancers, including TNBC, and represents a potential new therapeutic target. CDK9 increases RNA Polymerase II (Pol II) activity, which facilitates sustained expression of short-lived oncogenic and anti-apoptotic proteins. However, pre-clinical evaluation of CDK9 as a therapeutic target has been hampered by the poor selectivity of existing CDK9 inhibitors (CDK9i). Here, we report a novel CDK9i; D11-8, which exhibits high potency against CDK9 (Ki = 8 nM) and displays remarkable selectivity over other CDKs and human kinases. D11-8 inhibited TNBC cell line proliferation,, induced G2/M cell cycle arrest, and increased apoptosis. Mechanistically, D11-8 inhibited CDK9; reducing Pol II phosphorylation, down-regulating expression of proto-oncogene MYC and anti-apoptotic marker MCL1, and dramatically inducing Pol II promoter-proximal pausing at MYC, G2/M checkpoint, and E2F2 target genes. D11-8 was further validated for TNBC in vivo, and inhibited TNBC cell line tumour growth without toxicity. To further elucidate the cancer cell specificity of D11-8, normal breast tissue was collected from women undergoing reduction mammoplasty surgery and treated with D11-8 ex vivo as patient-derived explants. High doses of D11-8 (2.7 µM) had no effect on the proliferative capacity of normal breast epithelial cells (Ki67 positivity), and tissues appeared histologically normal. Collectively, these data demonstrate that D11-8 effectively inhibits CDK9 in TNBC cell lines, resulting in growth inhibition without short-term toxicity.
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2013-11-08 | E-GEOD-52194 | biostudies-arrayexpress