Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Homo sapiens

ABSTRACT: FBXW7 circular RNA Encodes a Novel Tumor Suppressive Protein in human Cells

PROVIDER: PRJNA355185 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR5133906_1.fastq.gz	Fastqsanger.gz
	SRR5133906_2.fastq.gz	Fastqsanger.gz
	SRR5133907_1.fastq.gz	Fastqsanger.gz
	SRR5133907_2.fastq.gz	Fastqsanger.gz

Items per page:

1 - 4 of 4

Similar Datasets

Homo sapiens

Project description:PINT circular RNA Encodes a Novel Tumor Suppressive Protein in human Cells

| PRJNA402091 | ENA

Homo sapiens

Project description:PINT circular RNA Encodes a Novel Tumor Suppressive Protein in human Cells

| PRJNA449410 | ENA

Homo sapiens

Project description:PINT circular RNA Encodes a Novel Tumor Suppressive Protein in human Cells

| PRJNA401369 | ENA

Cancer-associated FBXW7 loss is synthetic lethal with pharmacological targeting of CDC

Project description:The FBXW7 tumour suppressor is commonly mutated, deleted or hypermethylated in a variety of cancer histologies. The tumour suppressive role of the FBXW7 protein has been ascribed to its ability to drive the ubiquitination and degradation of oncoproteins via its role as a substrate recognition subunit of SCF complexes that mediate E3 ubiquitin ligation. Despite this molecular understanding, therapeutic approaches that target tumoural FBXW7 defects do not exist. To identify candidate vulnerabilities put in place by FBXW7 dysfunction, we carried out genome-wide CRISPR-Cas9 screens, focussed RNA interference screens and whole proteome mass spectrometry profiling in multiple FBXW7 wild type and defective isogenic cell systems. These identified candidate FBXW7 synthetic lethal effects, including those involving SCF-related proteins (e.g. CAND1), proteins involved in the response to replication fork stress (ATR, RAD9A and CHEK1) and also proteins involved in replication licencing such as CDC7 and its substrate GINS4. The ATR, CHEK1 and CDC7 synthetic lethal effects were confirmed using drug-like small molecule inhibitors. Integration of proteomic profiling data indicated that FBXW7 defective cells express elevated levels of the replication factor RIF1. Functional experiments showed that FBXW7 vs. CDC7 synthetic lethality is RIF1 dependent and explained by RIF1 being required for CDC7 inhibitor-induced replication fork stalling. The delineation of FBXW7 synthetic lethal effects we describe here could serve as the starting point for subsequent drug discovery and/or development in this area.

2024-06-16 | PXD043904 | Pride

FBXW7 is a defining driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition

Project description:Fbxw7 is a tumor supressor frequently mutated in endometrial cancer. To analyze the signaling pathways that can be altered by Fbxw7 we compared RNA expression in the presence or absence of Fbxw7 in mouse endometrial cancer cells deficient for Fbxw7 and Pten.

2019-11-11 | GSE138490 | GEO

Homo sapiens

Project description:Natural circular RNA encodes regulatory small peptides in Mammalian cells

| PRJNA300953 | ENA

circBAX encode a novel protein

Project description:circBax, a kind of circular RNA, encode novel protein

2024-11-27 | PXD058360 |

Loss of Fbxw7 triggers mammary tumorigenesis associated with E2F/c-Myc activation and Trp53 mutation

Project description:Fbw7 is a tumor suppressor protein that regulates the degradation of a multitude of oncogenic substrates, such as c-Jun, c-Myc, Notch1 intracellular domain, and cyclin E. Loss of FBXW7 expression is relatively common in breast cancer. Despite this, the effect of FBXW7 loss on breast tumorigenesis has not been examined. We demonstrate here that loss of FBXW7 is sufficient for breast tumorigenesis. Many of Fbw7’s substrates are transcription factors or are closely linked to transcription factor pathways. As loss of Fbw7 results in upregulation of multiple substrates, we set out to determine which, if any of these transcription factor pathways predominate early after Fbw7 loss and after tumorigenesis. To address this, we employed genome-wide RNA sequencing to examine transcription factor pathway alterations early after FBXW7 loss in non-tumor breast epithelial cells as well as after prolonged FBXW7 loss, in tumor samples. We demonstrate an early upregulation of E2F and c-Myc pathways that is reinforced upon tumorigenesis. These findings suggest E2F and c-Myc as important targetable pathways in Fbw7 low breast cancer patients.

2020-07-15 | GSE144690 | GEO

Targeting mitochondrial translation overcomes multidrug resistance in FBXW7-deficient cells

Project description:FBXW7 is one of the most frequently mutated tumor suppressors, the deficiency of which has been associated with resistance to some anticancer therapies. Through bioinformatic analyses and genome-wide CRISPR screens, we here reveal that FBXW7 deficiency leads to multi-drug resistance (MDR), to a bigger extent than well-established MDR-drivers such as ABCB1. Proteomic data from FBXW7-deficient cells and human cancer samples identify the upregulation of mitochondrial function as a hallmark of FBXW7 deficiency, which has been previously linked to an increased resistance to chemotherapy. Accordingly, genetic or chemical targeting of mitochondria is preferentially toxic for FBXW7-deficient cells. For instance, targeting mitochondrial translation with the antibiotic Tigecycline efficiently kills FBXW7-deficient cells in vitro and in vivo, by a mechanism that involves activation of the Integrated Stress Response (ISR). Searching for additional drugs that overcome MDR in FBXW7-deficient cells, we found several targeted therapies such as Erlotinib, Dasatinib or Vemurafenib which unexpectedly also activate the ISR. Together, our study reveals that one of the most frequent mutations in cancer reduces the sensitivity to the vast majority of available therapies, and identifies a general principle to overcome such resistance.

2022-06-08 | PXD029981 | Pride

RNA-seq of poly(A)-/ribo- or poly(A)+ RNAs from human and mouse ES cells

Project description:We have used RNA-seq to examine circular RNAs from poly(A)-/ribo- RNAs in human and mouse embryonic stem cells In order to identify novel circular RNAs from different species

2014-08-19 | E-GEOD-60467 | biostudies-arrayexpress

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