Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer.
Drug Resist Updat
; 73: 101059, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38295753
ABSTRACT
Patients with bladder cancer (BCa) frequently acquires resistance to platinum-based chemotherapy, particularly cisplatin. This study centered on the mechanism of cisplatin resistance in BCa and highlighted the pivotal role of lactylation in driving this phenomenon. Utilizing single-cell RNA sequencing, we delineated the single-cell landscape of Bca, pinpointing a distinctive subset of BCa cells that exhibit marked resistance to cisplatin with association with glycolysis metabolism. Notably, we observed that H3 lysine 18 lactylation (H3K18la) plays a crucial role in activating the transcription of target genes by enriching in their promoter regions. Targeted inhibition of H3K18la effectively restored cisplatin sensitivity in these cisplatin-resistant epithelial cells. Furthermore, H3K18la-driven key transcription factors YBX1 and YY1 promote cisplatin resistance in BCa. These findings enhance our understanding of the mechanisms underlying cisplatin resistance, offering valuable insights for identifying novel intervention targets to overcome drug resistance in Bca.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
/
Cisplatino
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Drug Resist Updat
Assunto da revista:
ANTINEOPLASICOS
Ano de publicação:
2024
Tipo de documento:
Article