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

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机构： [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. [6]Department of Urology, Ganzhou People's Hospital, Ganzhou, PR China.

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关键词： Bladder cancer Cisplatin resistance Histone lactylation Transcription factors

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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.Copyright © 2024 Elsevier Ltd. All rights reserved.

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出版当年[2023]版中科院分区表Review为是的期刊

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大类 | 1 区医学

小类 | 1 区药学

最新[2025]版

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大类 | 1 区

医学

小类 | 1 区药学

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第一作者机构： [1]Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China.

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