Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Potent G-Quadruplex-Binding Compound QN-302 Downregulates S100P Gene Expression in Cells and in an In Vivo Model of Pancreatic Cancer

ABSTRACT: The Potent G-Quadruplex-Binding Compound QN-302 Downregulates S100P Gene Expression in Cells and in an In Vivo Model of Pancreatic Cancer

PROVIDER: PRJNA939626 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23641862.fastq.gz	Fastqsanger.gz
	SRR23641863.fastq.gz	Fastqsanger.gz
	SRR23641864.fastq.gz	Fastqsanger.gz
	SRR23641865.fastq.gz	Fastqsanger.gz
	SRR23641866.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 7

Similar Datasets

The Potent G-Quadruplex-Binding Compound QN-302 Downregulates S100P Gene Expression in Cells and in an In Vivo Model of Pancreatic Cancer

Project description:The naphthalene diimide compound QN-302, designed to bind to G-quadruplex DNA sequences within the promoter regions of cancer-related genes, has high anti-proliferative activity in pancreatic cancer cell lines and anti-tumor activity in several experimental models for the disease. We show here that QN-302 also causes down-regulation of the expression of the S100P gene and the S100P protein in cells and in vivo. This protein is well-established as being involved in key proliferation and motility pathways in several human cancers and has been identified as a potential biomarker in pancreatic cancer. The S100P gene contains 60 putative quadruplex-forming sequences, one of which is in the promoter region, 48 nucleotides up-stream from the transcription start site. We report biophysical and molecular modeling studies showing that this sequence forms a highly stable G-quadruplex in vitro, which is further stabilized by QN-302. We also report transcriptome analyses showing that S100P expression is highly upregulated in tissues from human pancreatic cancer tumors, compared to normal pancreas material. The extent of up-regulation is dependent on the degree of differentiation of tumor cells, with the most poorly differentiated, from more advanced disease, having the highest level of S100P expression. The experimental drug QN-302 is currently in pre-IND development (as of Q1 2023) and its ability to down-regulate S100P protein expression supports a role for this protein as a marker of therapeutic response in pancreatic cancer. These results are also consistent with the hypothesis that the S100P promoter G-quadruplex is a potential therapeutic target in pancreatic cancer at the transcriptional level for QN-302.

2023-04-01 | GSE226307 | GEO

The G-Quadruplex experimental drug QN-302 effectively impairs liposarcoma cell viability by inhibiting MDM2 expression and restoring p53 levels [CUT&Tag]

Project description:Well-differentiated (WD) and dedifferentiated (DD) liposarcomas (LPS) account for ~60% of all liposarcomas, characterized by 12q13–q15 region amplification and aberrant MDM2 expression. Current therapies are limited, particularly for advanced stages, leading to poor outcomes. G-quadruplexes (G4s), secondary structures in G-rich nucleic acid sequences, were identified in the MDM2 P2 promoter. We investigated MDM2 inhibition via small molecule G4 ligands. Laboratory and patient-derived LPS cell lines, and normal pre-adipocytes were analyzed using CUT&Tag, RNA-seq, cell viability, qRT-PCR, Western blot, siRNA, and nascent transcript assays. QN-302, a naphthalene diimide (NDI)-derivative, emerged as the most effective G4 ligand, significantly impairing WD/DDLPS cell growth in a dose-dependent manner by stabilizing MDM2 G4 at the P2 promoter, inhibiting polymerase progression, and reducing full-length MDM2 transcripts, leading to p53 accumulation and apoptotic cell death. In vivo, QN-302 reduced tumor volume and was well-tolerated in xenograft models. This novel therapeutic strategy to inhibit MDM2 and reactivate p53 in WD/DDLPS could extend to all tumors with wild-type TP53 and enhance anticancer efficacy when combined with other drugs.

2025-01-31 | GSE271822 | GEO

The G-Quadruplex experimental drug QN-302 effectively impairs liposarcoma cell viability by inhibiting MDM2 expression and restoring p53 levels [RNA-seq]

2025-01-31 | GSE271823 | GEO

The Potent G-Quadruplex-Binding Compound QN-302 Downregulates S100P Gene Expression in Cells and in an In Vivo Model of Pancreatic Cancer.

Project description:The naphthalene diimide compound QN-302, designed to bind to G-quadruplex DNA sequences within the promoter regions of cancer-related genes, has high anti-proliferative activity in pancreatic cancer cell lines and anti-tumor activity in several experimental models for the disease. We show here that QN-302 also causes downregulation of the expression of the S100P gene and the S100P protein in cells and in vivo. This protein is well established as being involved in key proliferation and motility pathways in several human cancers and has been identified as a potential biomarker in pancreatic cancer. The S100P gene contains 60 putative quadruplex-forming sequences, one of which is in the promoter region, 48 nucleotides upstream from the transcription start site. We report biophysical and molecular modeling studies showing that this sequence forms a highly stable G-quadruplex in vitro, which is further stabilized by QN-302. We also report transcriptome analyses showing that S100P expression is highly upregulated in tissues from human pancreatic cancer tumors, compared to normal pancreas material. The extent of upregulation is dependent on the degree of differentiation of tumor cells, with the most poorly differentiated, from more advanced disease, having the highest level of S100P expression. The experimental drug QN-302 is currently in pre-IND development (as of Q1 2023), and its ability to downregulate S100P protein expression supports a role for this protein as a marker of therapeutic response in pancreatic cancer. These results are also consistent with the hypothesis that the S100P promoter G-quadruplex is a potential therapeutic target in pancreatic cancer at the transcriptional level for QN-302.

| S-EPMC10051992 | biostudies-literature

The G-Quadruplex experimental drug QN-302 effectively impairs liposarcoma cell viability by inhibiting MDM2 expression and restoring p53 levels [CUT&Tag]

Project description:The G-Quadruplex experimental drug QN-302 effectively impairs liposarcoma cell viability by inhibiting MDM2 expression and restoring p53 levels [CUT&Tag]

| PRJNA1133696 | ENA

The G-Quadruplex experimental drug QN-302 effectively impairs liposarcoma cell viability by inhibiting MDM2 expression and restoring p53 levels [RNA-seq]

Project description:The G-Quadruplex experimental drug QN-302 effectively impairs liposarcoma cell viability by inhibiting MDM2 expression and restoring p53 levels [RNA-seq]

| PRJNA1133697 | ENA

The G-quadruplex experimental drug QN-302 impairs liposarcoma cell growth by inhibiting MDM2 expression and restoring p53 levels.

Project description:Well-differentiated/dedifferentiated liposarcomas (WD/DDLPSs) account for ∼60% of all liposarcomas. They have a poor prognosis due to limited therapeutic options. WD/DDLPSs are characterized by aberrant expression of mouse double minute 2 (MDM2), which forms G-quadruplexes (G4s) in its promoter. Here, we investigated the possibility of targeting WD/DDLPSs with small molecules against the MDM2 G4s. Among the molecules tested, the naphthalene diimide derivative QN-302 significantly impaired WD/DDLPS cell growth and its activity strikingly paralleled cell-specific G4 abundance as measured by CUT&Tag and RNA sequencing analysis. QN-302 stabilized MDM2 G4s at the P2 inducible promoter and prevented polymerase progression from the constitutive P1 promoter, thereby inhibiting the formation of full-length MDM2 transcripts. This resulted in the accumulation of p53 through the p53-MDM2 autoregulatory feedback loop, ultimately leading to apoptotic cell death. In patient-derived xenograft mouse models, QN-302 treatment reduced tumour volume distribution and was well tolerated. We have identified a novel and effective therapeutic strategy to reduce MDM2 expression and promote p53 reactivation in tumours harbouring wild-type TP53, such as WD/DDLPSs.

| S-EPMC11822379 | biostudies-literature

QN-302 demonstrates opposing effects between i-motif and G-quadruplex DNA structures in the promoter of the S100P gene.

Project description:GC-rich sequences can fold into G-quadruplexes and i-motifs and are known to control gene expression in many organisms. The potent G-quadruplex experimental anticancer drug QN-302 down-regulates a number of cancer-related genes, in particular S100P. Here we show this ligand has strong opposing effects with i-motif DNA structures and is one of the most potent i-motif destabilising agents reported to date. QN-302 down-regulates the expression of numerous cancer-related genes by pan-quadruplex targeting. QN-302 exhibits exceptional combined synergistic effects compared to many other G-quadruplex and i-motif interacting compounds. This work further emphasises the importance of considering G-quadruplex and i-motif DNA structures as one dynamic system.

| S-EPMC10732280 | biostudies-literature

miRNA analyses of genetic factors and the role of carotenoid accumulation in adductor muscles of QN Orange scallops

Project description:QN Orange scallop was interspecific hybrids with orange adductor muscles. Previous studies shown the accumulation of carotenoids was present in QN Orange scallops. In this study, analysis of miRNA expression profiles was performed to explore possibly regulatory patterns in carotenoid accumulation in adductor muscles of QN Orange scallops. Based on small RNA sequencing, a total of 3289 miRNAs and 91 differential expression miRNAs were identified between white and orange adductor muscles, respectively. GO and KEGG enrichment analysis of target genes of DE miRNA enriched in the transmembrane transporter activity-related pathways, kinase activity-related pathways, signal transduction-related pathways, ABC transporters, Retinol metabolism, lipid related metabolism and calcium signaling pathway.

2024-11-10 | GSE248569 | GEO

G-Quadruplex structures are stable and detectable in human genomic DNA.

Project description:The G-quadruplex is an alternative DNA structural motif that is considered to be functionally important in the mammalian genome. Herein, we address the hypothesis that G-quadruplex structures can exist within double-stranded genomic DNA using a G-quadruplex-specific probe. An engineered antibody is employed to enrich for DNA containing G-quadruplex structures, followed by deep sequencing to detect and map G-quadruplexes at high resolution in genomic DNA from human breast adenocarcinoma cells. Our high sensitivity structure-based pull-down strategy enables the isolation of genomic DNA fragments bearing a single as well as multiple G-quadruplex structures. Stable G-quadruplex structures are found in sub-telomeres, gene bodies and gene regulatory regions. For a sample of identified target genes, we show that G-quadruplex stabilizing ligands can modulate transcription. These results confirm the existence of G-quadruplex structures and their persistence in human genomic DNA. Four independent libraries have been enriched in DNA G-quadruplex structures using a G-quadruplex-specific probe. One genomic input library was sequenced as control. Deep-sequencing of these libraries allowed the mapping of G-quadruplexes on the genome.

2013-05-08 | E-GEOD-45241 | 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