Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The MYC-YBX1 Circuit in Maintaining Stem-like Vincristine-Resistant Cells in Rhabdomyosarcoma

ABSTRACT: Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma that causes significant devastation, with no effective therapy for relapsed disease. The mechanisms behind treatment failures are poorly understood. Our study showed that treatment of RMS cells with vincristine led to an increase in CD133-positive stem-like resistant cells. Single cell RNAseq analysis revealed that MYC and YBX1 were among the top-scoring transcription factors in CD133-high expressing cells. Targeting MYC and YBX1 using CRISPR/Cas9 reduced stem-like characteristics and viability of the vincristine-resistant cells. MYC and YBX1 showed mutual regulation, with MYC binding to the YBX1 promoter and YBX1 binding to MYC mRNA. The MYC inhibitor MYC361i synergized with vincristine to reduce tumor growth and stem-like cells in a zebrafish model of RMS. MYC and YBX expression showed a positive correlation in RMS patients, and high MYC expression correlated with poor survival. Targeting the MYC-YBX1 axis holds promise for improving survival in RMS patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE232536 | GEO | 2023/05/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The MYC-YBX1 Circuit in Maintaining Stem-like Vincristine-Resistant Cells in Rhabdomyosarcoma

Project description:The MYC-YBX1 Circuit in Maintaining Stem-like Vincristine-Resistant Cells in Rhabdomyosarcoma

| PRJNA972687 | ENA

Improving anti-tumor efficacy of low-dose Vincristine in rhabdomyosarcoma via the combination therapy with FOXM1 inhibitor RCM1.

Project description:Rhabdomyosarcoma (RMS) is a highly metastatic soft-tissue sarcoma that often develops resistance to current therapies, including vincristine. Since the existing treatments have not significantly improved survival, there is a critical need for new therapeutic approaches for RMS patients. FOXM1, a known oncogene, is highly expressed in RMS, and is associated with the worst prognosis in RMS patients. In the present study, we found that the combination treatment with specific FOXM1 inhibitor RCM1 and low doses of vincristine is more effective in increasing apoptosis and decreasing RMS cell proliferation in vitro compared to single drugs alone. Since RCM1 is highly hydrophobic, we developed innovative nanoparticle delivery system containing poly-beta-amino-esters and folic acid (NPFA), which efficiently delivers RCM1 to mouse RMS tumors in vivo. The combination of low doses of vincristine together with intravenous administration of NPFA nanoparticles containing RCM1 effectively reduced RMS tumor volumes, increased tumor cell death and decreased tumor cell proliferation in RMS tumors compared to RCM1 or vincristine alone. The combination therapy was non-toxic as demonstrated by liver metabolic panels using peripheral blood serum. Using RNA-seq of dissected RMS tumors, we identified Chac1 as a uniquely downregulated gene after the combination treatment. Knockdown of Chac1 in RMS cells in vitro recapitulated the effects of the combination therapy. Altogether, combination treatment with low doses of vincristine and nanoparticle delivery of FOXM1 inhibitor RCM1 in a pre-clinical model of RMS has superior anti-tumor effects and decreases CHAC1 while reducing vincristine toxicity

2023-01-18 | GSE223149 | GEO

Transcription profiling of cultured human ovarian cancer cells vincristine-sensitive parental ovarian tumor cell line (SKOV3) and its highly vincristine-resistant derivative

Project description:Gene expression profiles were assessed for vincristine-sensitive parental ovarian tumor cell line (SKOV3) and its highly vincristine-resistant derivative (SKVCR 2.0) Experiment Overall Design: Duplicate gene expression microarray experiments were undertaken for each of SKOV3 and SKVCR 2.0. Comparative analysis between these two groups defined genes activated in vincristine resistance

2008-06-15 | E-GEOD-7556 | biostudies-arrayexpress

Transcription profiling of primary ALL cells (B-lineage) resistant to vincristine by the MTT in vitro sensitivity assay

Project description:primary ALL cells (B-lineage) resistant to vincristine by the MTT in vitro sensitivity assay

2008-06-15 | E-GEOD-658 | biostudies-arrayexpress

Transcription profiling of primary ALL cells (B-lineage) resistant to vincristine by the MTT in vitro sensitivity assay

Project description:primary ALL cells (B- and T-lineage) resistant to vincristine by the MTT in vitro sensitivity assay

2008-06-14 | E-GEOD-649 | biostudies-arrayexpress

Ybx1 is required for Survival of Leukemia Stem Cells and the Development of Chronic Myeloid Leukemia

Project description:Chronic myeloid leukemia (CML) is a myeloproliferative disorder derived from hematopoietic stem cells (HSCs) that harbor Philadelphia chromosome (Ph chromosome). Leukemia stem cells (LSCs) in CML are insensitive to TKIs treatment, and are responsible for disease relapse. However, the molecular mechanisms for LSCs survival remains elusive. Here we show that YBX1 plays an important role in regulating survival of CML LSCs. We find that YBX1 expression is significantly increased in CML cells. Using CML patient-derived cell lines and a BCR-ABL-induced CML mouse model, we confirm that YBX1 is required for survival maintenance of LSCs. Deletion of YBX1 impairs the propagation of CML through impairing cell cycle and inducing apoptosis of LSCs. Mechanistically, we find that YBX1 regulates expression of apoptosis-related genes, and YBX1 binds MYC and BCL2 transcripts. YBX1 loss decreases expression of MYC and BCL2 by accelerating their mRNA decay. In addition, restoration of MYC and BCL2 efficiently rescue the defects of YBX1-deficient CML cells. Overall, our findings reveal a critical role of YBX1 in maintaining survival of CML LSCs, which may provide a rationale for targeting YBX1 in CML treatment.

2022-03-27 | GSE199304 | GEO

Gene expression signatures of chemotherapy-induced neuropathy induced by vincristine

Project description:Vincristine, oxaliplatin, and cisplatin are commonly prescribed chemotherapeutic agents for the treatment of several cancer types. However, a main side-effect is chemotherapy-induced peripheral neuropathy (CIPN), which may lead to decreased quality of life, changes in chemotherapeutic treatment or even treatment cessation. Although painful symptoms associated with CIPN are faithfully recapitulated by mouse models, there is limited knowledge of how these drugs affect the expression of genes in peripheral sensory neurons. The present study carried out a transcriptomic analysis of dorsal root ganglia isolated from mice treated with vincristine, oxaliplatin, and cisplatin with a view to gain insight into the comparative pathophysiological mechanisms of CIPN. RNA-Seq using 75-nucleotide single end runs revealed 368, 295 and 256 differential expressed genes (DEGs) induced by treatment with vincristine, oxaliplatin and cisplatin, respectively. Although there were many similarities in DEGs between chemotherapeutic agents, only 5 genes were dysregulated in all groups. Cell type enrichment analysis (CTEA) and gene set enrichment analysis (GSEA) showed predominant effects on genes associated with the immune system after treatment with vincristine, while oxaliplatin treatment affected mainly neuronal genes. Treatment with cisplatin resulted in a mixed inflammatory and neuropathic gene expression signature. Only ‘regulation of transport’ and ‘response to external stimuli’ were gene ontology terms shared between all treatments. These results provide insight into the recruitment of innate and adaptive immune responses to DRG tissue and indicate enhanced neuro-inflammatory processes following administration of vincristine, oxaliplatin, and cisplatin. These gene expression signatures may provide insight into novel drug targets for treatment of CIPN.

2019-06-01 | GSE125001 | GEO

Exploring the Mechanism of Resistance to vincristine in Breast Cancer Cells through Transcriptome Sequencing Technology

Project description:Breast cancer has replaced lung cancer as the leading cancer globally, but various chemotherapy drugs for breast cancer are prone to generate resistance, especially in patients with distant metastases who are susceptible to multiple chemotherapy drug resistance, these always leading to treatment failure. vincristine (VCR) is an alkaloid extracted from Catharanthus roseus and is often used in combination with other chemotherapy drugs to treat various types of cancer, including breast cancer. Recently, we conducted research on the development of resistance to VCR using transcriptome sequencing technology. Firstly, we used the gradient increase of VCR concentration to produce a VCR-resistant breast cancer cell line. Mechanistically, we further extracted RNA from the VCR-resistant breast cancer cell line and sequenced the transcriptome. Further analysis showed changes in various gene expression levels in the VCR-resistant breast cancer cell line. Meanwhile, the analysis of splicing events also indicated that variable splicing events change in the VCR-resistant breast cancer cell line. Further validation showed that multiple gene expression levels, including 1L1B, were altered in the VCR-resistant breast cancer cell line, and these gene expression changes were related to VCR resistance. Our results provide a theoretical basis for exploring the mechanism of VCR resistance clinically.

2023-09-12 | GSE241356 | GEO

CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype

Project description:Metastatic human colon carcinoma cell lines LS411N and SW620 were cultured in the presence of increased concentration of 5-FU. The selected stable cell lines (LS411N-5FU-R and SW620-5FU-R) are CD133+ that are resistant to 5-FU. However, FACS-sorted CD133+ cells from LS411N and SW620 are not resistant to 5-FU, suggesting that only a subset of CD133+ cells are 5-FU-resistant colon cancer stem cells. A global gene expression profiling was performed to identify differentiated expressed genes between LS411N-CD133+ cells and LS411N-5FU-R, and between SW620-CD133+ and SW620-5FU-R cells. These differentially expressed genes are potentially responsible for the colon cancer stem cell phenotypes and chemoresistance.

2016-12-20 | GSE76489 | GEO

Comparison of gene expression between CD133+ and CD133- SW620 human colon cancer cells

Project description:CD133 has been widely used for identification and isolation of cancer stem cells in tumors although its role as a marker for cancer stem cell is still controversial . We isolated the CD133+ and CD133- cells from SW620 human colon cancer cell line and compared their biological characteristics, such as tumorigenicity,drug sensitivity, etc. Our study revealed that CD133+ SW620 cells were more tumorigenic and resistant to anti-cancer drugs. Correspondingly, they displayed different gene expression profile. However, it was observed that CD133- cells and CD133+ cells could mutually convert, indicating that CD133 expression was under dynamic and reversible regulations which might impose significant infulence on cells behaviors. Thus, our data challenge the role of CD133 as a marker for cancer stem cell.

2010-07-29 | GSE23295 | 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