BibTex format
@article{Robinson:2025:10.1186/s13059-025-03654-y,
author = {Robinson, J and Flint, G and Garner, I and Galli, S and Maher, TE and Kuimova, MK and Vilar, R and McNeish, IA and Brown, R and Keun, H and Di, Antonio M},
doi = {10.1186/s13059-025-03654-y},
journal = {Genome Biology},
title = {G-quadruplex structures regulate long-range transcriptional reprogramming to promote drug resistance in ovarian cancer cells},
url = {http://dx.doi.org/10.1186/s13059-025-03654-y},
volume = {26},
year = {2025}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Background:Epigenetic evolution is a common mechanism used by cancer cells to evade the therapeutic effects of drug treatment. In ovarian cancers, epigenetically driven resistance is thought to be responsible for many late-stage patient deaths. DNA secondary structures called G-quadruplex (G4) are emerging aspotential epigenetic marks of relevance to cancer evolution, but their prevalence and distribution in ovarian cancer models has never been investigated before.Results:Here, we describe the first investigation of the role of G4s in the epigenetic regulation of drug-resistant ovarian cancer cells. Through genome-wide mapping of G4s in paired drug-sensitive and drug-resistant cell lines, we find that increased G4 accumulation is associated with enhanced transcription of signalling pathways previously established to promote drug-resistant states, including genes involved in the epithelial to mesenchymal transition and WNT signalling. In contrast to previous studies, the expression-enhancing effects of G4s are not found at gene promoters, but intergenic and intronic regions, indicating that G4s can promote long-range transcriptional regulation in drug-resistant cells. Furthermore, we discover that clusters of G4s (super-G4s) are associated with particularly high levels of transcriptional enhancement thatsurpass the effects of super-enhancers, which act as well-establishedregulatory sites in many cancers. Finally, we demonstrate that targeting G4s with small molecules results in significant down-regulation of pathways associated with drug-resistance, resulting inresensitisation of resistant cells to chemotherapy agents. Conclusions:These findings indicate that G4 structures are critical for the epigenetic regulatory networks of drug resistant cells and represent a promising target to treat drug-tolerant ovarian cancer.
AU - Robinson,J
AU - Flint,G
AU - Garner,I
AU - Galli,S
AU - Maher,TE
AU - Kuimova,MK
AU - Vilar,R
AU - McNeish,IA
AU - Brown,R
AU - Keun,H
AU - Di,Antonio M
DO - 10.1186/s13059-025-03654-y
PY - 2025///
SN - 1474-7596
TI - G-quadruplex structures regulate long-range transcriptional reprogramming to promote drug resistance in ovarian cancer cells
T2 - Genome Biology
UR - http://dx.doi.org/10.1186/s13059-025-03654-y
VL - 26
ER -