2. Academic Validation
  3. Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer

Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer

  • Drug Resist Updat. 2024 Mar:73:101059. doi: 10.1016/j.drup.2024.101059.
Fei Li 1,  Henghui Zhang 1,  Yuan Huang 1,  Dongqing Li 1,  Zaosong Zheng 1,  Kunfeng Xie 1,  Chun Cao 1,  Qiong Wang 1,  Xinlei Zhao 1,  Zehai Huang 1,  Shijun Chen 1,  Haiyong Chen 2,  Qin Fan 3,  Fan Deng 4,  Lina Hou 5,  Xiaolin Deng 6,  Wanlong Tan 7
Affiliations

Affiliations

  • 1 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China.
  • 2 School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong R619, 3 Sassoon Road, Pokfulam, Hong Kong, SAR China.
  • 3 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, PR China.
  • 4 Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, PR China.
  • 5 Department of Healthy Management, Nanfang Hospital, Southern Medical University, Guangzhou, PR China. Electronic address: [email protected].
  • 6 Department of Urology, Ganzhou People's Hospital, Ganzhou, PR China. Electronic address: [email protected].
  • 7 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China. Electronic address: [email protected].
PMID: 38295753 DOI: 10.1016/j.drup.2024.101059
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.

Keywords

Bladder cancer; Cisplatin resistance; Histone lactylation; Transcription factors.

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