Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Systematic analyses of RNA-binding proteins uncover therapeutically promising vulnerabilities in osteosarcoma

ABSTRACT: Systematic analyses of RNA-binding proteins uncover therapeutically promising vulnerabilities in osteosarcoma

PROVIDER: PRJNA1032883 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR26545451_1.fastq.gz	Fastqsanger.gz
	SRR26545451_2.fastq.gz	Fastqsanger.gz
	SRR26545452_1.fastq.gz	Fastqsanger.gz
	SRR26545452_2.fastq.gz	Fastqsanger.gz
	SRR26545453_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 28

Similar Datasets

Systematic analyses of RNA-binding proteins uncover therapeutically promising vulnerabilities in osteosarcoma

Project description:Osteosarcoma (OS) is the most common primary malignant bone tumor with a strong tendency to metastasize, limiting the prognosis of affected patients. Genomic, epigenomic and transcriptomic analyses have demonstrated the exquisite molecular complexity of this tumor, but haven't sufficiently defined the underlying mechanisms or identified promising therapeutic targets. To systematically explore RNA-protein interactions relevant to OS, we defined the RNA interactomes together with the full proteome and the transcriptome of cells from five malignant bone tumors (four osteosarcomata and one malignant giant cell tumor of the bone) and from normal mesenchymal stem cells and osteoblasts. These analyses uncovered both systematic changes of RNA-binding activity common to all osteosarcomata and individual alterations that were observed in only a subset of tumors. Functional analyses especially revealed a vulnerability of these tumors to translation inhibition and a positive feedback circuit involving the RNA-binding protein IGF2BP3 and the transcription factor Myc which affected cellular translation and OS cell viability. Our results provide novel and potentially clinically relevant insights into a previously uncharted molecular landscape of osteosarcoma.

2024-02-27 | GSE246405 | GEO

Enhanced combination treatment on osteosarcoma by mitigating drug-induced oncogenic signaling pathway activation

Project description:Osteosarcoma is a prevalent primary malignant bone tumor in children and young adults, with limited progress in improving survival rates for metastatic or recurrent cases. Kinase inhibitors emerged as potential treatment for osteosarcoma due to the critical role of kinases regulating network. However, single-agent kinase inhibitors often face challenges due to the activation of compensatory oncogenic signaling pathways, which can undermine treatment efficacy. In this study, a systematic combination screening of kinase inhibitors was further conducted in osteosarcoma cells. Among 190 pair-wise combinations, 44 exhibited strong synergistic antitumor efficacy. Notably, the combination of the ALK inhibitor Ceritinib and the FLT3 inhibitor Crenolanib showed significant synergistic effects against osteosarcoma cell lines, patient-derived organoids in vitro, and xenograft models in vivo. This combination also effectively mitigated the compensatory activation of oncogenic signaling pathways, a common resistance mechanism to single-agent therapies. Our findings provide compelling evidence that dual kinase inhibition targeting ALK and FLT3 can effectively exploit pharmacological vulnerabilities in osteosarcoma, suggesting a promising therapeutic strategy for clinical application. This combinatorial approach could potentially overcome the limitations of single-agent therapies and improve outcomes for patients with osteosarcoma. Further clinical evaluation is warranted to confirm these preclinical results.

2024-10-29 | GSE278302 | GEO

CBX5 loss drives EGFR inhibitor resistance and results in therapeutically actionable vulnerabilities in lung cancer

Project description:CBX5 loss drives EGFR inhibitor resistance and results in therapeutically actionable vulnerabilities in lung cancer

| PRJNA471762 | ENA

Human models of NUP98-KDM5A megakaryocytic leukemia contribute to uncover new biomarkers and therapeutic vulnerabilities

Project description:Human models of NUP98-KDM5A megakaryocytic leukemia contribute to uncover new biomarkers and therapeutic vulnerabilities

| PRJNA508928 | ENA

MeDIP chip from ZOS and ZOSM osteosarcoma cell lines

Project description:Epigenetic change of genes expression, including hypomethylation-linked activation of oncogenes and hypermethylation-associated inactivation of tumor suppressor genes, can affect almost all the cellular signaling pathways that participate in cancer initiation and progression. Unlike genetic alterations, epigenetic changes are potentially reversible, making them attractive and promising targets for therapeutic intervention. Studies indicated that abnormal DNA methylation is involved in dysregulation of cell cycle, apoptosis, proliferation and differentiation of osteosarcoma. However, epigenetic mechanisms of osteosarcoma metastasis remain largely unknown. MeDIP chips are performed in ZOS and ZOSM—two syngeneic primary human osteosarcoma cell lines with low and high metastatic potential which are established in our lab

2015-08-25 | E-GEOD-55961 | biostudies-arrayexpress

MeDIP chip from ZOS and ZOSM osteosarcoma cell lines

2015-08-25 | GSE55961 | GEO

Mapping in silico genetic networks of tumour suppressor gene to uncover novel functional associations and cancer cell vulnerabilities

Project description:Cancers harbouring loss-of-function (LOF) alterations in tumour suppressor genes lack targeted therapies, thus alternative means to characterise gene function and identify vulnerabilities in these cancer cells are required. Here, we map the in silico genetic networks of KMT2D, a frequently mutated tumour suppressor gene, to demonstrate its utility in uncovering novel functional associations and vulnerabilities in cancer cells with tumour suppressor gene LOF alterations. In silico KMT2D networks revealed associated with histone modification, DNA replication, metabolism, and immune response. We identified synthetic lethal (SL) candidates encoding exising therapeutic targets. Analysing patient data from The Cancer Genome Atlas (TCGA) and the Personalized OncoGenomics Project (NCT021556210), we showed dysregulated pathways associated with SL candidates and elevated immune checkpoint response markers in KMT2DLOF cases, bringing forth evidence supporting KMT2D as a biomarker for immune checkpoint inhibitors. Our study presents a framework for identifying targetable vulnerabilities in cancers with tumour suppressor gene alterations.

2024-10-18 | PXD048272 | Pride

Super-enhancer-associated oncogenes as novel therapeutic targets in osteosarcoma (ChIP-seq)

Project description:Despite the development of diagnostic and advanced treatment strategies, the prognosis of patients with osteosarcoma remains poor. A limited understanding of the pathogenesis of osteosarcomas has impeded any improvement in patient outcomes over the past 4 decades. It is thus urgent to identify novel effective targets and treatment regimens for osteosarcoma patients. In this study we delineated the super-enhancer landscape in osteosarcoma cells on the basis of H3K27ac signal intensity by ChIP-Seq and found that super-enhancer-associated genes contribute to the malignant potential of osteosarcoma. THZ2, a novel small molecular inhibitor, shows a powerful anti-osteosarcoma ability through suppress super-enhancer-associated genes selectively. Utilizing the characteristics of super-enhancers in cancer cells, we identified 5 critical super-enhancer-associated oncogenes. With the comparative and retrospective analysis in large numbers of human specimens from patients, these 5 oncogenes were observed closely related with patient prognosis. Our findings determined that targeting super-enhancer-associated oncogenes with transcriptional inhibitor, THZ2, was a promising therapeutic strategy in osteosarcoma, and provided novel candidate targets for patients with osteosarcoma.

2019-12-27 | GSE134604 | GEO

Super-enhancer-driven MLX mediates redox balance maintanance via SLC7A11 in osteosarcoma

Project description:A systematic analysis of super-enhancers identified MLX as a potential oncogene in osteosarcoma. Knockdown of MLX impaired tumor aggressiveness in vitro and in vivo, suggesting oncogenic properties of MLX. Mechanistically, silencing of MLX downregulates SLC7A11, a key gene encoding glutamate/cystine antiporter, to attenuate the uptake of cystine and interrupt the redox balance, leading to ferroptotic cell death. Pharmacological inhibition of SLC7A11 triggered massive ferroptosis and caused impaired tumor growth, providing a promising approach for osteosarcoma treatment.

2023-08-08 | GSE220173 | GEO

Canine osteosarcoma tissues vs. normal bone

Project description:Leveraging the conserved cancer genomes across mammals has the potential to transform driver gene discovery in orphan cancers. Here, we combine cross-species genomics with validation across human-dog-mouse systems to uncover a new osteosarcoma driver genes. This widely applicable cross-species approach serves as a platform to expedite search of cancer drivers in rare human malignancies offering new targets for cancer therapy.

2021-03-08 | GSE111637 | 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