articleAdvanced ScienceMar 13, 2024GOLD OA

Histone H3K9 Lactylation Confers Temozolomide Resistance in Glioblastoma via LUC7L2‐Mediated MLH1 Intron Retention

YQYue QuZWZhao WangYSYixiong ShenYLYufei LanXZXiangyang Zhong

Zhujiang Hospital · Southern Medical University

PubMed
Indexed incrossrefdoajpubmed

Abstract

Temozolomide (TMZ) resistance remains the major obstacle in the treatment of glioblastoma (GBM). Lactylation is a novel post-translational modification that is involved in various tumors. However, whether lactylation plays a role in GBM TMZ resistance remains unclear. Here it is found that histone H3K9 lactylation (H3K9la) confers TMZ resistance in GBM via LUC7L2-mediated intron 7 retention of MLH1. Mechanistically, lactylation is upregulated in recurrent GBM tissues and TMZ-resistant cells, and is mainly concentrated in histone H3K9. Combined multi-omics analysis, including CUT&Tag, SLAM-seq, and RNA-seq, reveals that H3K9 lactylation is significantly enriched in the LUC7L2 promoter and activates LUC7L2…

Citation impact

115
total citations
FWCI
44.80
Percentile
100%
References
45
Citations per year

Authors

14

Topics & keywords

Topics
Keywords
  • Temozolomide
  • Cancer research
  • Histone
  • Methyltransferase
  • Downregulation and upregulation
  • Glioblastoma
  • Biology
  • Gene
UN Sustainable Development Goals
  • Good health and well-being
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