Genome-wide analysis of senecent MCF7 cells induced by irridiation and ectopic overexpression of p21
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE108895 | GEO | 2019/04/25
REPOSITORIES: GEO
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Project description:Genome-wide analysis of senecent MCF7 cells induced by irridiation and ectopic overexpression of p21
| PRJNA429037 | ENA
Project description:A mass spectrometry-based proteomics analysis was performed to study the protein binders of p21 in MCF7 cells during the progression and maintenance of cellular senescence.
2024-06-02 | PXD042908 | Pride
Project description:Elevated mitochondrial biogenesis and metabolism represent key features of breast cancer stem cells (CSCs), whose propagation is conducive to disease onset and progression. Therefore, interfering with mitochondria biology and function may be regarded as a useful approach to eradicate CSCs. Here, we used the breast cancer cell line MCF7 as a model system to interrogate how mitochondrial fission contributes to the development of mitochondrial dysfunction toward the inhibition of metabolic flux and stemness. We generated an isogenic MCF-7 cell line transduced with Mitochondrial Fission Factor (MCF7-MFF), which is primarily involved in mitochondrial fission. We evaluated the biochemical, molecular and functional properties of MCF7-MFF cells, as compared to control MCF7 cells transduced with the empty vector (MCF7-Control). We observed that MFF over-expression reduces both mitochondrial mass and activity, as evaluated using the mitochondrial probes MitroTracker Red and MitoTracker Orange, respectively. The analysis of metabolic flux using the Seahorse XFe96 revealed the inhibition of OXPHOS and glycolysis in MCF7-MFF cells, suggesting that increased mitochondrial fission may impair the biochemical properties of these organelles. Notably, CSCs activity, assessed by 3D-tumorsphere assays, was reduced in MCF7-MFF cells. A similar trend was observed for the activity of ALDH, a well-established marker of stemness. We conclude that enhanced mitochondrial fission may compromise CSCs propagation, through the impairment of mitochondrial function, possibly leading to a quiescent cell phenotype. Unbiased proteomic analysis revealed that proteins involved in mitochondrial dysfunction, oxidative stress-response, fatty acid metabolism and hypoxia signaling are among the most highly up-regulated in MCF7-MFF cells. Of note, integrated analysis of top regulatory networks obtained from unbiased proteomics in MCF7-MFF cells predicts that this cell phenotype activates signaling systems and effectors involved in the inhibition of cell survival and adhesion, together with the activation of specific breast cancer cell death programs. Overall, our study shows that unbalanced and abnormal activation of mitochondrial fission may drive the impairment of mitochondrial metabolic function, leading to inhibition of CSC propagation, and the activation of quiescence programs. Exploiting the potential of mitochondria to control pivotal events in tumor biology may, therefore, represent a useful tool to prevent disease progression.
2020-10-16 | PXD020802 | Pride
Project description:A PTHrP construct expressing full-length secreted PTHrP (-36-139aa) was stably expressed in MCF7 cells. The goal of the study was to determine the gene targets of PTHrP in human MCF7 breast cancer cells.
2018-05-30 | GSE110713 | GEO
Project description:Targeting senescent cells for therapeutic purposes is gaining momentum across various organ systems. However, concerns about potential off-target effects have been raised. Previous studies have shown that removing senescent cells expressing high levels of p16 (p16high) can hinder processes like wound healing. Here, we identify a distinct senescent cell population during dermal wound healing characterized by high expression level of p21 (p21high) using the p21-Cre mouse model. Using a standard cutaneous injury model, we find that eliminating p21high cells can expedite wound closure, in contrast to the effects of removing p16high cells. Through Xenium, a single cell spatial imaging platform, we show that p21high cells are distinct from p16high cells, with p21high cells mainly comprising fibroblasts, immune cells, keratinocytes, and endothelial cells with a pro-inflammatory profile. Moreover, inhibition of NF-kB signaling specifically from p21high cells partially contributes to the accelerated wound healing rates. These findings highlight the heterogeneity of senescent cells during wound healing responses within the skin and likely in other conditions.
2024-10-07 | GSE278611 | GEO
Project description:PTHrP overexpression in MCF7 cells
| PRJNA434402 | ENA
Project description:Targeting senescent cells for therapeutic purposes is gaining momentum across various organ systems. However, concerns about potential off-target effects have been raised. Previous studies have shown that removing senescent cells expressing high levels of p16 (p16high) can hinder processes like wound healing. Here, we identify a distinct senescent cell population during dermal wound healing characterized by high expression level of p21 (p21high) using the p21-Cre mouse model. Using a standard cutaneous injury model, we find that eliminating p21high cells can expedite wound closure, in contrast to the effects of removing p16high cells. Through Xenium, a single cell spatial imaging platform, we show that p21high cells are distinct from p16high cells, with p21high cells mainly comprising fibroblasts, immune cells, keratinocytes, and endothelial cells with a pro-inflammatory profile. Moreover, inhibition of NF-kB signaling specifically from p21high cells partially contributes to the accelerated wound healing rates. These findings highlight the heterogeneity of senescent cells during wound healing responses within the skin and likely in other conditions.
2024-10-01 | GSE278527 | GEO
Project description:Cellular senescence is a permanent state of cell cycle arrest that protects the organism from tumorigenesis and regulates tissue integrity upon damage and during tissue remodeling. However, accumulation of senescent cells in tissues during aging contributes to age-related pathologies. A deeper understanding of the mechanisms regulating the viability of senescent cells is therefore required. Here we show that the CDK inhibitor p21 (CDKN1A) maintains the viability of DNA damage-induced senescent cells.
2017-06-13 | GSE98240 | GEO
Project description:As we clarified before, the FOXP3 gene is an X-linked tumor suppressor gene in mammary carcinoma in both human and mouse. We also clarified that the ERBB2 and SKP2 oncogenes were transcriptionally under control of the FOXP3 gene product in mammary epithelial cells. In order to further clarify the FOXP3 down stream target genes in human breast cancer cells, we planed to conduct a microarray analysis of FOXP3-induced gene expression profiling. MCF7, a human breast cancer cell line, with FOXP3-tet-off system was cultured with and without Doxycyclin for 2 days. In the MCF7 cell cultured without Dox, the FOXP3 transcript was significantly induced as compared to the MCF7 cultured with Dox. Total RNA from MCF7 with and wihtout Dox were extracted by Qiagen's RNeasy column and they were applied to Affymetrix Human U133 2.0 array according to the manufacture's protocol. We clarified as yet unknown FOXP3 target genes in human epithelial cells, e.g., the p21 gene, by this analysis.
2009-08-12 | E-MTAB-73 | biostudies-arrayexpress
Project description:Long noncoding RNAs regulating diverse cellular processes implicate in many diseases. Here, we report the identification of a novel long intergenic noncoding RNA, Linc-ASEN, expressed in prematurely senescent cells, that associates with UPF1 and represses cellular senescence by reducing p21 production transcriptionally and post-transcriptionally. The Linc-ASEN-UPF1 complex suppressed p21 transcription by recruiting Polycomb Repressive Complex 1 (PRC1) and PRC2 to the p21 locus, and thereby preventing binding of the transcriptional activator p53 on the p21 promoter. Moreover, the Linc-ASEN-UPF1 complex repressed p21 expression post-transcriptionally by lowering p21 mRNA stability in association with DCP1A. Accordingly, Linc-ASEN levels were found inversely correlated with p21 mRNA levels in tumor tissues from patient-derived xenograft mice, in various human cancer tissues, and in aged mice tissues. Our studies reveal that Linc-ASEN prevents cellular senescence by reducing the transcription and stability of p21 mRNA in concert with UPF1, and suggest that Linc-ASEN might be a potential therapeutic target in processes influenced by senescence, including cancer.
2019-09-24 | GSE128397 | GEO