1. THAP3 recruits SMYD3 to OXPHOS genes and epigenetically promotes mitochondrial respiration in hepatocellular carcinoma.
- Author
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Zi-Hao Wang, Jingyi Wang, Fuchen Liu, Sijun Sun, Quan Zheng, Xiaotian Hu, Zihan Yin, Chengmei Xie, Haiyan Wang, Tianshi Wang, Shengjie Zhang, and Yi-Ping Wang
- Subjects
TRANSCRIPTION factors ,CELL respiration ,CANCER cell proliferation ,LIVER cancer ,OXIDATIVE phosphorylation - Abstract
Mitochondria harbor the oxidative phosphorylation (OXPHOS) system to sustain cellular respiration. However, the transcriptional regulation of OXPHOS remains largely unexplored. Through the cancer genome atlas (TCGA) transcriptome analysis, transcription factor THAP domain-containing 3 (THAP3) was found to be strongly associated with OXPHOS gene expression. Mechanistically, THAP3 recruited the histone methyltransferase SET and MYND domain-containing protein 3 (SMYD3) to upregulate H3K4me3 and promote OXPHOS gene expression. The levels of THAP3 and SMYD3 were altered by metabolic cues. They collaboratively supported liver cancer cell proliferation and colony formation. In clinical human liver cancer, both of them were overexpressed. THAP3 positively correlated with OXPHOS gene expression. Together, THAP3 cooperates with SMYD3 to epigenetically upregulate cellular respiration and liver cancer cell proliferation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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