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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author Mujie Yuan
Kexin Wang
Baoxing Pang
Haijun Lu
Shuai Jiang
Kai Song
Zongxuan He
Jing Deng
Jianjun Yang
Lin Wang
author_facet Mujie Yuan
Kexin Wang
Baoxing Pang
Haijun Lu
Shuai Jiang
Kai Song
Zongxuan He
Jing Deng
Jianjun Yang
Lin Wang
author_sort Mujie Yuan
collection DOAJ
description 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.
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institution Kabale University
issn 1420-9071
language English
publishDate 2025-06-01
publisher Springer
record_format Article
series Cellular and Molecular Life Sciences
spelling doaj-art-16fac49c0c57405d91fdb6770d4b86e32025-08-20T03:45:11ZengSpringerCellular and Molecular Life Sciences1420-90712025-06-0182111210.1007/s00018-025-05765-yPreliminary investigation of the epigenetic regulation of KMT2D via H3K4me1/H3K27ac in oral squamous cell carcinomaMujie Yuan0Kexin Wang1Baoxing Pang2Haijun Lu3Shuai Jiang4Kai Song5Zongxuan He6Jing Deng7Jianjun Yang8Lin Wang9Department of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao UniversityDepartment of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao UniversityDepartment of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao UniversityDepartment of Radiation Oncology, the Affiliated Hospital of Qingdao UniversityDepartment of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao UniversityDepartment of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao UniversityDepartment of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao UniversitySchool of Stomatology, Qingdao UniversityDepartment of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao UniversityDepartment of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao UniversityAbstract 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.https://doi.org/10.1007/s00018-025-05765-yKMT2DOral squamous cell carcinomaHistone modificationKLF7TPO
spellingShingle Mujie Yuan
Kexin Wang
Baoxing Pang
Haijun Lu
Shuai Jiang
Kai Song
Zongxuan He
Jing Deng
Jianjun Yang
Lin Wang
Preliminary investigation of the epigenetic regulation of KMT2D via H3K4me1/H3K27ac in oral squamous cell carcinoma
Cellular and Molecular Life Sciences
KMT2D
Oral squamous cell carcinoma
Histone modification
KLF7
TPO
title Preliminary investigation of the epigenetic regulation of KMT2D via H3K4me1/H3K27ac in oral squamous cell carcinoma
title_full Preliminary investigation of the epigenetic regulation of KMT2D via H3K4me1/H3K27ac in oral squamous cell carcinoma
title_fullStr Preliminary investigation of the epigenetic regulation of KMT2D via H3K4me1/H3K27ac in oral squamous cell carcinoma
title_full_unstemmed Preliminary investigation of the epigenetic regulation of KMT2D via H3K4me1/H3K27ac in oral squamous cell carcinoma
title_short Preliminary investigation of the epigenetic regulation of KMT2D via H3K4me1/H3K27ac in oral squamous cell carcinoma
title_sort preliminary investigation of the epigenetic regulation of kmt2d via h3k4me1 h3k27ac in oral squamous cell carcinoma
topic KMT2D
Oral squamous cell carcinoma
Histone modification
KLF7
TPO
url https://doi.org/10.1007/s00018-025-05765-y
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