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 | GSE271823 | GEO

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

2025-01-31 | GSE271822 | GEO

seq-302-32369_H3K9me2_ojIs9_YA_germline

Project description:modENCODE_submission_6325 This submission comes from a modENCODE project of Jason Lieb. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: The focus of our analysis will be elements that specify nucleosome positioning and occupancy, control domains of gene expression, induce repression of the X chromosome, guide mitotic segregation and genome duplication, govern homolog pairing and recombination during meiosis, and organize chromosome positioning within the nucleus. Our 126 strategically selected targets include key histone modifications and histone variants. We will integrate information generated with existing knowledge on the biology of the targets and perform ChIP-seq analysis on mutant and RNAi extracts lacking selected target proteins. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

2013-08-28 | GSE50331 | GEO

[PDMR] [PDX] [384148-302-R] Merkel Cell Carcinoma

Project description: Not available

| S-CMO4475 | biostudies-other

Genomic landscape of liposarcoma.

Project description: Not available

| S-EPMC4767443 | biostudies-literature

Pdx-1 or Pdx-1-VP16 protein transduction induces beta-cell gene expression in liver-stem WB cells.

Project description: Not available

| S-EPMC2637887 | biostudies-literature