Preliminary investigation of the epigenetic regulation of KMT2D via H3K4me1/H3K27ac in oral squamous cell carcinoma

Abstract Histone lysine methyltransferase 2D (KMT2D/MLL4) critically modulates gene expression by methylating and acetylating histones H3K4/H3K27, thereby regulating the expression of specific target genes. Although KMT2D is highly mutated in a variety of cancers, its role in the progression of oral...

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Main Authors: Mujie Yuan, Kexin Wang, Baoxing Pang, Haijun Lu, Shuai Jiang, Kai Song, Zongxuan He, Jing Deng, Jianjun Yang, Lin Wang
Format: Article
Language:English
Published: Springer 2025-06-01
Series:Cellular and Molecular Life Sciences
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Online Access:https://doi.org/10.1007/s00018-025-05765-y
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Summary:Abstract Histone lysine methyltransferase 2D (KMT2D/MLL4) critically modulates gene expression by methylating and acetylating histones H3K4/H3K27, thereby regulating the expression of specific target genes. Although KMT2D is highly mutated in a variety of cancers, its role in the progression of oral squamous cell carcinoma (OSCC) remains unclear. The purpose of this study was to reveal the significance of KMT2D expression in OSCC and to preliminarily explore the regulatory effect of KMT2D on the expression of OSCC-related genes by influencing histone modifications. In this study, through immunohistochemistry, gene editing, RNA-Seq, ATAC-seq, CHI-Seq and combined analysis, the following conclusions were drawn: KMT2D plays a role in histone modification, chromatin opening and gene transcription translation in oral squamous cell cancer cells. Integrated multi-omics data analysis indicated that KLF7 and TPO may be target genes regulated by KMT2D.
ISSN:1420-9071