Abstract | BACKGROUND: RESULTS: 429 chromatin regulators were screened by a machine learning approach and aberrant expression of SMYD3 was found to be closely associated with OSCC formation and poor prognosis. Data profiling of single-cell and tissue demonstrated that upregulated SMYD3 significantly correlated with aggressive clinicopathological features of OSCC. Alterations in copy number and DNA methylation patterns may contribute to SMYD3 overexpression. Functional experimental results suggested that SMYD3 enhanced cancer cell stemness and proliferation in vitro and tumor growth in vivo. SMYD3 was observed to bind to the High Mobility Group AT-Hook 2 (HMGA2) promoter and elevated tri-methylation of histone H3 lysine 4 at the corresponding site was responsible for transactivating HMGA2. SMYD3 also was positively linked to HMGA2 expression in OSCC samples. Furthermore, treatment with the SMYD3 chemical inhibitor BCI-121 exerted anti- tumor effects. CONCLUSIONS:
Histone methyltransferase activity and transcription-potentiating function of SMYD3 were found to be essential for tumorigenesis and the SMYD3-HMGA2 is a potential therapeutic target in OSCC.
|
Authors | Zongcheng Yang, Fen Liu, Zongkai Li, Nianping Liu, Xinfeng Yao, Yu Zhou, Liyu Zhang, Pan Jiang, Honghong Liu, Lingming Kong, Chuandong Lang, Xin Xu, Jihui Jia, Takahito Nakajima, Wenchao Gu, Lixin Zheng, Zhihong Zhang |
Journal | Clinical epigenetics
(Clin Epigenetics)
Vol. 15
Issue 1
Pg. 92
(05 26 2023)
ISSN: 1868-7083 [Electronic] Germany |
PMID | 37237385
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2023. The Author(s). |
Chemical References |
- histone H3 trimethyl Lys4
- Histone-Lysine N-Methyltransferase
- Histones
- SMYD3 protein, human
|
Topics |
- Humans
- Carcinogenesis
(genetics)
- Cell Line, Tumor
- Cell Transformation, Neoplastic
(genetics)
- DNA Methylation
- Gene Expression Regulation, Neoplastic
- Histone-Lysine N-Methyltransferase
(metabolism)
- Histones
(metabolism)
- Mouth Neoplasms
(genetics)
- Squamous Cell Carcinoma of Head and Neck
(genetics)
|