Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting cell cycle and apoptosis to overcome chemoresistance in AML

ABSTRACT: Targeting cell cycle and apoptosis to overcome chemoresistance in AML

PROVIDER: PRJNA847626 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR19608579.fastq.gz	Fastqsanger.gz
	SRR19608580.fastq.gz	Fastqsanger.gz
	SRR19608581.fastq.gz	Fastqsanger.gz
	SRR19608582.fastq.gz	Fastqsanger.gz
	SRR19608583.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Targeting cell cycle and apoptosis to overcome chemoresistance in AML

Project description:A genome-wide CRISPR knockout screen investigating resistance to doxorubicin and cytarabine (Dox/AraC) in human AML cell lines identified gene knockout of cyclin dependent kinase inhibitor 2A (CDKN2A) as contributing to resistance. To investigate the therapeutic potential of upregulating CDKN2A expression using WM-1119 and further elucidate its mechanism of action, we performed RNA-seq on WM-1119- (or vehicle control) treated OCI-AML3 cells with or without CRISPR mediated genetic depletion of CDKN2A.

2022-11-22 | GSE205802 | GEO

Targeting IFN-γ-inducible lysosomal thiol reductase Overcomes Chemoresistance in AML through Regulating the ROS-mediated mitochondrial damage

Project description:Our work demonstrated that the inhibition of GILT increases AML chemo-sensitivity through elevating ROS level and induce oxidative mitochondrial damage-mediated apoptosis, and inhibition of the PI3K/Akt/NRF2 pathway enhances the intracellular oxidative state by disrupting redox homeostasis. Our study provides a potentially effective way to overcome chemoresistance of AML.

2021-03-31 | PXD025114 |

TNFAIP8 promotes AML chemoresistance by activating ERK signaling pathway through interaction with Rac1

Project description:The tumor necrosis factor induced protein 8 (TNFAIP8), a novel anti-apoptotic molecule, has been implicated in chemoresistance of several types of neoplasms, but its role in AML remains to be elucidated. In this study, upregulated TNFAIP8 expression was found in human AML patients and cell lines. E74 like ETS transcription factor 1 (ELF1) was identified to contribute to its aberrant expression. Forced expression of TNFAIP8 protected cells from apoptosis induced by chemotherapeutic agents and increased drug resistance. Importantly, the leukemia-promoting action of TNFAIP8 was mediated by sustaining activity of the extracellular signal-regulated kinase (ERK) signaling pathway through an interaction with Rac family small GTPase 1 (Rac1). In vivo experiments showed that TNFAIP8 suppression lowered leukemia infiltration and improved survival. Taken together, our data provide a molecular basis for the role of TNFAIP8 in chemoresistance and progression of AML and highlight the unique function of TNFAIP8 as an attractive therapeutic target.

2020-08-19 | GSE154253 | GEO

Induction of a timed metabolic collapse to overcome cancer chemoresistance

Project description:Induction of a timed metabolic collapse to overcome cancer chemoresistance

| PRJNA578674 | ENA

Targeting Dual-specificity Phosphatase 23 to Overcome Chemoresistance and Stem Cell-like Behavior in Non-small Cell Lung Cancer Cells

Project description:Chemoresistance poses a significant challenge in treating non-small cell lung cancer (NSCLC), often leading to poor outcomes. This resistance is closely linked to cancer stem cell (CSC)-like characteristics, including the ability to evade anoikis. In this study, we identified dual-specificity phosphatase 23 (DUSP23) as a key molecule involved in regulating CSC traits and chemoresistance. DUSP23 expression was significantly elevated in cell clusters grown under ultra-low adhesion (ULA) conditions that mimic CSC-promoting environments. Silencing DUSP23 reduced the formation of these clusters, suppressed the expression of the stemness markers SOX2, and enhanced anoikis sensitivity. Additionally, in cisplatin-resistant NSCLC cells, knockdown of DUSP23 decreased invasive behavior and induced apoptosis. These findings suggest that DUSP23 plays a pivotal role in maintaining CSC-like properties and chemoresistance by regulating SOX2. Targeting DUSP23 could offer a novel approach to overcome treatment resistance and improve outcomes for patients with NSCLC.

2025-01-31 | GSE288032 | GEO

An alternative transcription factor isoform controls AML chemoresistance

Project description:An alternative transcription factor isoform controls AML chemoresistance

| PRJNA1139820 | ENA

Intra-leukemic interferon signaling suppresses expansion and mediates chemoresistance in human AML

Project description:Intra-tumoral heterogeneity can impact the competitive fitness and chemoresistance of individual cancer cells. In acute myeloid leukemia (AML), both genetic and functional heterogeneity contribute to chemoresistance, resulting in relapse after chemotherapy. While the role of cell-extrinsic factors such as interactions with non-leukemic cells has been described for AML relapse, whether interactions between cancer cells affects chemoresistance is not fully known. Here, we demonstrate that a dominant leukemic fraction can suppress the proliferation and expansion of other leukemic cells and that this suppression is reversible. We show that this suppression is mediated in part by both type I and type II intra-leukemic interferon (IFN) signaling and dependent on BST2. Importantly, blocking antibodies to type II IFN receptor activated the cycling of this suppressed cell fraction and sensitized the cells to subsequent chemotherapy treatment. Our findings suggest that interactions between functionally heterogeneous leukemic fractions can affect competitive fitness and treatment response, highlighting IFN signaling as a potential therapeutic target to counter chemoresistance.

2025-10-05 | GSE307827 | GEO

A novel lncRNA FUAT1/TNS4 axis confers chemoresistance by suppressing ROS-mediated apoptosis in gastric cancer

Project description:Reactive oxygen species (ROS) play a vital role in conveying the cytotoxicity and resistance of most chemo-drugs. Thus, a better understanding of the detailed activities against oxidative stress in cancer cells may provide novel insights into the discovery of common mechanisms underlying chemoresistance. In this study, taking advantage of a customized screening strategy based on transcriptome sequencing (RNA-Seq) technology, we identified a novel lncRNA, designated FUAT1, as a key non-genetic player that participates in ROS-mediated intrinsic chemoresistance in gastric cancer (GC) cells. The role of the FUAT1 regulatory axis in chemoresistance was further explored by using a series of in vitro and in vivo assays, including gain/loss-of-function and rescue experiments. Mechanistically, FUAT1 could upregulate TNS4 by sponging miR-140-5p, allowing GC cells to survive upon chemotherapy via inhibition of ROS-mediated apoptosis. Clinically, the FUAT1/TNS4 regulatory axis is negatively associated with overall and progression-free survival in gastric and colon cancer patients treated with 5-FU adjuvant chemotherapy. Our findings touch on a fundamental adaptive mechanism for the survival of cancer cells upon chemotherapy, providing a novel insight into the development of strategies to overcome chemoresistance.

2023-11-30 | GSE236987 | GEO

Fatty acid oxidation protects cancer cells from apoptosis through increasing mitochondrial membrane lipids

Project description:<p>Overcoming resistance to chemotherapies remains a major unmet need for cancers such as triple negative breast cancer (TNBC). Therefore, mechanistic studies to provide insight for drug development are urgently needed to overcome TNBC therapy resistance. Recently, an important role of fatty acid β-Oxidation (FAO) in chemoresistance has been shown. But how FAO might mitigate tumor cell apoptosis by chemotherapy is unclear. Here, we show that elevated FAO activates STAT3 by acetylation via elevated acetyl-CoA. Acetylated STAT3 upregulates expression of long-chain acyl-CoA synthetase 4 (ACSL4), resulting in increased phospholipid synthesis. Elevating phospholipids in mitochondrial membranes leads to heightened mitochondrial integrity, which in turn overcomes chemotherapy-induced tumor cell apoptosis. Conversely, in both cultured tumor cells and xenograft tumors, enhanced cancer cell apoptosis by inhibiting ASCL4 or specifically targeting acetylated-STAT3 is associated with a reduction in phospholipids within mitochondrial membranes. This study demonstrates a critical mechanism underlying tumor cell chemoresistance.</p>

2022-05-31 | MTBLS4709 | MetaboLights

SIRT3 SUMOylation confers AML chemoresistance via down-regulation of HES1 dependent fatty acid oxidation

Project description:SIRT3 deacetylase is a critical mitochondrial regulator for mitochondrial metabolism reprogramming and ROS production, and is involved in the regulation of chemoresistance in AML. SIRT3 is a SUMOylated protein, with de-SUMOylation by SENP1, resulted in enhancement of its deacetylase activity. However, the molecular mechanism of de-SUMOylation mediated SIRT3 activation, which may lead to reinforced AML chemoresistance, remains poorly understood. In the current study, we demonstrated that SIRT3 SUMOylation was attenuated by cytarabine, and de-SUMOylation prevented SIRT3 from proteasome degradation. SIRT3 de-SUMOylation was capable of reprogramming mitochondrial biogenesis, and subsequently inhibited mitochondrial ROS production. Furthermore, RNA-seq revealed that expression of a collection of genes was altered by SIRT3 de-SUMOylation, among which the transcription factor HES1, a downstream substrates of Notch1 signaling pathway, was significantly downregulated by SIRT3K288R, the de-SUMOylated and constitutively active mutant of SIRT3. HES1-dependent FAO was inhibited by SIRT3 de-SUMOylation. Moreover, cytarabine synergized with the SENP1 inhibitor momodrin-Ic to eradicate AML blasts in vitro and in xenografts mice models. In summary, the current study revealed a novel role of SIRT3 SUMOylation in regulating chemoresistance in AML via HES1-dependent FAO, which may provide a rationale for SIRT3 SUMOylation-targeted intervention to improve the chemotherapies in AML.

2022-08-17 | GSE179617 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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