ArticleClinical epigenetics2019
Histone methyltransferases EHMT1 and EHMT2 (GLP/G9A) maintain PARP inhibitor resistance in high-grade serous ovarian carcinoma.
Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 90 citations in OpenAlex.
- Inhibiting CXCR2 Remodels the Tumor Microenvironment and Blunts Tumor Progression and Dissemination of High-Grade Serous Carcinoma.Cancer research communications · 2026Article
- Metabolic drivers of genome instability in cancer: mechanisms and therapeutic opportunities.Experimental hematology & oncology · 2026Review
- Pulpitis Transiently Affect Hepatic Bone Morphogenetic Protein 9 Expression by Lipopolysaccharide.International dental journal · 2026Article
- Natural Compounds as Epimodulators in Epithelial Ovarian Cancer.Epigenomes · 2026Review
- PARP1 and PARP2 are dispensable for DNA repair by microhomology-mediated end-joining at double-ended DSBs.Nucleic acids research · 2026Article
- PARylation-centric crosstalk: orchestrating immune evasion and multidrug resistance in ovarian cancer.Frontiers in immunology · 2026Review
- SM08502-Mediated β-Catenin Repression Synergizes with Olaparib to Inhibit Tumor Progression.Cancer research communications · 2025Article
- The interplay of DNA damage, epigenetics and tumour heterogeneity in driving cancer cell fitness.Nature communications · 2025Review
- Targeting RAD52 overcomes PARP inhibitor resistance in preclinicalbioRxiv : the preprint server for biology · 2025Article
- Article
- Comprehensive dataset of interactors for the entire PARP family using TurboID proximity labeling.Scientific data · 2025Article
- NSD3 protein methylation and stabilization transforms human ES cells into variant state.Life science alliance · 2025Article
- Unveiling drug resistance pathways in high-grade serous ovarian cancer(HGSOC): recent advances and future perspectives.Frontiers in immunology · 2025Review
- EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell-Dependent Manner.Molecular cancer research : MCR · 2024Article
- The Spatial Structure of the Tumor Immune Microenvironment Can Explain and Predict Patient Response in High-Grade Serous Carcinoma.Cancer immunology research · 2024Article
- A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication.PLoS biology · 2024Article
- Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.Molecular cancer therapeutics · 2024Article
- Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma.Cancer research communications · 2024Article
- GLP and G9a histone methyltransferases as potential therapeutic targets for lymphoid neoplasms.Cancer cell international · 2024Review
- EHMT2-mediated transcriptional reprogramming drives neuroendocrine transformation in non-small cell lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundEuchromatic histone-lysine-N-methyltransferases 1 and 2 (EHMT1/2, aka GLP/G9A) catalyze dimethylation of histone H3 lysine 9 (H3K9me2) and have roles in epigenetic silencing of gene expression. EHMT1/2 also have direct roles in DNA repair and are implicated in chemoresistance in several cancers. Resistance to chemotherapy and PARP inhibitors (PARPi) is a major cause of mortality in high-grade serous ovarian carcinoma (HGSOC), but the contribution of the epigenetic landscape is unknown.
resultsTo identify epigenetic mechanisms of PARPi resistance in HGSOC, we utilized unbiased exploratory techniques, including RNA-Seq and mass spectrometry profiling of histone modifications. Compared to sensitive cells, PARPi-resistant HGSOC cells display a global increase of H3K9me2 accompanied by overexpression of EHMT1/2. EHMT1/2 overexpression was also observed in a PARPi-resistant in vivo patient-derived xenograft (PDX) model. Genetic or pharmacologic disruption of EHMT1/2 sensitizes HGSOC cells to PARPi. Cell death assays demonstrate that EHMT1/2 disruption does not increase PARPi-induced apoptosis. Functional DNA repair assays show that disruption of EHMT1/2 ablates homologous recombination (HR) and non-homologous end joining (NHEJ), while immunofluorescent staining of phosphorylated histone H2AX shows large increases in DNA damage. Propidium iodide staining and flow cytometry analysis of cell cycle show that PARPi treatment increases the proportion of PARPi-resistant cells in S and G2 phases, while cells treated with an EHMT1/2 inhibitor remain in G1. Co-treatment with PARPi and EHMT1/2 inhibitor produces an intermediate phenotype. Immunoblot of cell cycle regulators shows that combined EHMT1/2 and PARP inhibition reduces expression of specific cyclins and phosphorylation of mitotic markers. These data suggest DNA damage and altered cell cycle regulation as mechanisms of sensitization. RNA-Seq of PARPi-resistant cells treated with EHMT1/2 inhibitor showed significant gene expression changes enriched in pro-survival pathways that remain unexplored in the context of PARPi resistance, including PI3K, AKT, and mTOR.
conclusionsThis study demonstrates that disrupting EHMT1/2 sensitizes HGSOC cells to PARPi, and suggests a potential mechanism through DNA damage and cell cycle dysregulation. RNA-Seq identifies several unexplored pathways that may alter PARPi resistance. Further study of EHMT1/2 and regulated genes will facilitate development of novel therapeutic strategies to successfully treat HGSOC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.