| RRC ID |
85991
|
| 著者 |
Noberini R, Robusti G, Vai A, Savoia EO, Jodice MG, Bertalot G, Çat B, Pallavicini I, Bonizzi G, Capra M, Sangalli CA, Zambelli F, Fusco N, Pece S, Pavesi G, Minucci S, Bonaldi T.
|
| タイトル |
A histone-centric multi-omics study shows that increased H3K4 methylation sustains triple-negative breast cancer phenotypes.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Altered histone post-translational modifications are frequently associated with cancer. Here, we apply mass-spectrometry to study the epigenetic landscapes of breast cancer subtypes, with a particular focus on triple-negative breast cancers (TNBCs), a heterogeneous group lacking well-defined molecular targets and effective therapies. The analysis of over 200 tumors reveals epigenetic signatures that discriminate TNBCs from the other BC subtypes, and that distinguish TNBC patients with different prognoses. Employing a multi-OMICs approach integrating epigenomics, transcriptomics, and proteomics data, we investigate the mechanistic role of increased H3K4 methylation in TNBCs, demonstrating that H3K4me2 sustains the expression of genes associated with the TNBC phenotype. Through CRISPR-mediated editing, we establish a causal relationship between H3K4me2 and gene expression for several targets. Furthermore, treatment with H3K4 methyltransferase inhibitors reduce TNBC cell growth in vitro and in vivo. Collectively, our results unravel a novel epigenetic pathway implicated in TNBC pathogenesis and suggest new opportunities for targeted therapy.
|
| 巻・号 |
16(1)
|
| ページ |
8716
|
| 公開日 |
2025-9-30
|
| DOI |
10.1038/s41467-025-63745-z
|
| PII |
10.1038/s41467-025-63745-z
|
| PMID |
41028718
|
| PMC |
PMC12484688
|
| MeSH |
Animals
Cell Line, Tumor
Cell Proliferation
Epigenesis, Genetic
Epigenomics
Female
Gene Expression Regulation, Neoplastic
Histone-Lysine N-Methyltransferase / antagonists & inhibitors
Histone-Lysine N-Methyltransferase / metabolism
Histones* / genetics
Histones* / metabolism
Humans
Methylation
Mice
Multiomics
Phenotype
Protein Processing, Post-Translational
Proteomics / methods
Triple Negative Breast Neoplasms* / genetics
Triple Negative Breast Neoplasms* / metabolism
Triple Negative Breast Neoplasms* / pathology
|
| IF |
12.121
|
| リソース情報 |
| 遺伝子材料 |
tFucci(CA)2/pCSII-EF (RDB15446) |
