Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression data of control, doxorubicin and/or Y27632 treated HeLa cells

ABSTRACT: In the treatment of cancer with chemotherapeutics, it has been observed that a significant amount of cancer cells turn into senescent cells. These senescent cells secrete several factors in their microenvironment called SASP. Therefore, recently, to develop the senolytic and/or senomorphic drugs, targeting the senescent cells gains importance as a new strategy for preventing the damage that senescent cancer cells cause. In the current work, we evaluated whether Rho/Rho kinase pathway has a potential to be used as a target pathway for the development of senolytic and/or senomorphic drugs, in doxorubicin-induced senescent cancer cell lines. We performed a whole-genome microarray analysis to determine how the expressions of SASP factors change in senescent cells and whether ROCK inhibition also causes changes in the expression of these factors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE160234 | GEO | 2021/04/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Chemo-senolytic therapeutic potential against angiosarcoma

Project description:Angiosarcoma is an aggressive soft-tissue sarcoma with a poor prognosis. Chemotherapy for this cancer typically employs paclitaxel, one of the taxanes (genotoxic drugs), although it has a limited effect due to chemoresistance for prolonged treatment. Here we examine a new angiosarcoma treatment approach that combines chemotherapeutic and senolytic agents. We first find that the chemotherapeutic drugs, cisplatin and paclitaxel, efficiently induce cellular senescence of angiosarcoma cells. Subsequent treatment with a senolytic agent, ABT-263, eliminates senescent cells through the activation of the apoptotic pathway. In addition, expression analysis indicates that senescence-associated secretory phenotype (SASP) genes are activated in senescent angiosarcoma cells and that ABT-263 treatment eliminates senescent cells expressing genes in the type-I interferon (IFN-I) pathway. Moreover, we show that cisplatin treatment alone requires a high dose to remove angiosarcoma cells, whereas a lower dose of cisplatin is sufficient to induce senescence, followed by the elimination of senescent cells by senolytic treatment. This study sheds light on a potential therapeutic strategy against angiosarcoma by combining a relatively low dose of cisplatin with the ABT-263 senolytic agent, which can help ease the deleterious side effects of chemotherapy.

2024-03-23 | GSE245935 | GEO

Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer

Project description:Accumulation of senescent cells in the tumour microenvironment can drive tumourigenesis in a paracrine manner through the senescence-associated secretory phenotype (SASP). Using a new p16-FDR mouse line, we show that macrophages and endothelial cells are the predominant senescent cell types in murine KRAS-driven lung tumours. Single cell transcriptomics identify a population of tumour-associated macrophages, expressing a unique array of pro-tumourigenic SASP factors and surface proteins, that are also present in normal aged lungs. Genetic or senolytic ablation of senescent cells, and macrophage depletion, result in a significant reduction in tumour burden and increased mouse survival of KRAS-driven lung cancer models. Of translational relevance, we reveal the presence of macrophages with senescent features in human lung premalignant lesions, but not in adenocarcinomas. Together, our results have uncovered a population of senescent macrophages contributing to the initiation and progression of lung cancer, thus opening potential therapeutic avenues and cancer preventative strategies.

2023-06-02 | GSE230054 | GEO

Whole-Body Senescent Cell Clearance Alleviates Age-Related Brain Inflammation and Cognitive Impairment in Mice

Project description:Cellular senescence is characterized by an irreversible cell cycle arrest and a pro-inflammatory senescence-associated secretory phenotype (SASP), which is a major contributor to aging and age-related diseases. Clearance of senescent cells has been shown to improve brain function in mouse models of neurodegenerative diseases. However, it is still unknown whether senescent cell clearance alleviates cognitive dysfunction during the aging process. To investigate this, we first conducted single-nuclei and single-cell RNA-seq in the hippocampus from young and aged mice. We observed an age-dependent increase in p16Ink4a senescent cells, which was more pronounced in microglia and oligodendrocyte progenitor cells and characterized by a SASP. We then aged INK-ATTAC mice, in which p16Ink4a-positive senescent cells can be genetically eliminated upon treatment with the drug AP20187 and treated them either with AP20187 or with the senolytic cocktail Dasatinib and Quercetin. We observed that both strategies resulted in a decrease in p16Ink4a exclusively in the microglial population, resulting in reduced microglial activation and reduced expression of SASP factors. Importantly, both approaches significantly improved cognitive function in aged mice. Our data provide proof-of-concept for senolytic interventions’ being a potential therapeutic avenue for alleviating age-associated cognitive impairment.

2021-02-06 | GSE161340 | GEO

Muscle injury induces a transient senescence-like state that is required for myofiber growth during muscle regeneration

Project description:Cellular senescence is the irreversible arrest of normally dividing cells and is driven by the cell cycle inhibitors Cdkn2a, Cdkn1a, and Trp53. Senescent cells are implicated in chronic diseases and tissue repair through their increased secretion of proinflammatory factors known as the senescence-associated secretory phenotype (SASP). Here, we use spatial transcriptomics and single-cell RNA sequencing (scRNAseq) to demonstrate that cells displaying senescent characteristics are “transiently" present within regenerating skeletal muscle and within the muscles of D2-mdx mice, a model of Muscular Dystrophy. Following injury, multiple cell types including macrophages and fibro-adipogenic progenitors (FAPs) upregulate senescent features such as senescence pathway genes, SASP factors, and senescence-associated beta-gal (SA-β-gal) activity. Importantly, when these cells were removed with ABT-263, a senolytic compound, satellite cells are reduced, and muscle fibers were impaired in growth and myonuclear accretion.

2022-10-11 | GSE214892 | GEO

Gene expression profiling of MDA-MB-231 cells incubated with therapy induced senescence secretome

Project description:TNBC, associated with poor prognosis and high tumour recurrence, are often treated with anti-mitotic drugs. However, cells may bypass treatment-induced cell death via mitotic slippage, resulting in multinucleated polyploid cells and senescence activation. Senescent cancer cells represent a population of residual disease and are highly secretory. The SASP elicited is enriched in soluble cytokines linked to tumor recurrence and distant metastasis. In contrast, sEVs derived from senescent cancer cells represent an underappreciated aspect of SASP and its mechanistic role in mediating paracrine effects remains poorly-understood. Here, we show senescent sEVs as a distinct population of SASP that could elicit anti-tumor activity.

2024-03-25 | GSE236953 | GEO

Gene expression profiling of MDA-MB-231 cells incubated with therapy induced senescence derived small extracellular vesicles

2024-03-25 | GSE238165 | GEO

Gene expression profiling of mouse breast tumor tissue after injection of 4T1 therapy-induced senesence derived sEVs

2024-03-25 | GSE237710 | GEO

Muscle injury induces a transient senescence-like state that is required for myofiber growth during muscle regeneration [Spatial Transcriptomics]

2022-10-14 | GSE215305 | GEO

Homo sapiens

Project description:Achilles Heels of Senescent Cells: From Transcriptome to Senolytic Drugs

| PRJNA276172 | ENA

The YAP-TEAD complex promotes senescent cell survival by lowering endoplasmic reticulum stress [scRNA-seq_mouse]

Project description:Sublethal cell damage can trigger a complex adaptive program known as senescence, characterized by growth arrest, resistance to apoptosis, and a senescence-associated secretory phenotype (SASP). As senescent cells accumulating in aging organs are linked to many age-associated diseases, senotherapeutic strategies are actively sought to eliminate them. Here, a whole-genome CRISPR knockout screen revealed that proteins in the YAP-TEAD pathway influenced senescent cell viability. Accordingly, treating senescent cells with a drug that inhibited this pathway, Verteporfin (VPF), selectively triggered apoptotic cell death and derepressed DDIT4, in turn inhibiting mTOR. Reducing mTOR function in senescent cells diminished endoplasmic reticulum (ER) biogenesis, causing ER stress and apoptosis due to high demands on ER function by the SASP. Importantly, VPF treatment decreased senescent cell numbers in the organs of old mice and mice exhibiting doxorubicin-induced senescence. We present a novel senolytic strategy that eliminates senescent cells by hindering ER activity required for SASP production.

2023-07-13 | GSE232273 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data