The Histone Methyltransferase SETD8 Regulates the Expression of Tumor Suppressor Genes via H4K20 Methylation and the p53 Signaling Pathway in Endometrial Cancer Cells
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- Asako Kukita
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Kenbun Sone
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Syuzo Kaneko
- Division of Medical AI Research and Development, National Cancer Center Research Institute, Tokyo 104-0045, Japan
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- Eiryo Kawakami
- Graduate School of Medicine, Chiba University, Chiba 263-8522, Japan
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- Shinya Oki
- National Hospital Organization Tokyo Medical Center, Tokyo 152-8902, Japan
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- Machiko Kojima
- Tazuke Kofukai, Medical Research Institute, Kitano Hospital, Osaka 530-8480, Japan
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- Miku Wada
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Yusuke Toyohara
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Yu Takahashi
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Futaba Inoue
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Saki Tanimoto
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Ayumi Taguchi
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Tomohiko Fukuda
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Yuichiro Miyamoto
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Michihiro Tanikawa
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Mayuyo Mori-Uchino
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Tetsushi Tsuruga
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Takayuki Iriyama
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Yoko Matsumoto
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Kazunori Nagasaka
- Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Tokyo 173-0003, Japan
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- Osamu Wada-Hiraike
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Katsutoshi Oda
- Division of Integrated Genomics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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- Ryuji Hamamoto
- Division of Medical AI Research and Development, National Cancer Center Research Institute, Tokyo 104-0045, Japan
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- Yutaka Osuga
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
説明
<jats:p>The histone methyltransferase SET domain-containing protein 8 (SETD8), which methylates histone H4 lysine 20 (H4K20) and non-histone proteins such as p53, plays key roles in human carcinogenesis. Our aim was to determine the involvement of SETD8 in endometrial cancer and its therapeutic potential and identify the downstream genes regulated by SETD8 via H4K20 methylation and the p53 signaling pathway. We examined the expression profile of SETD8 and evaluated whether SETD8 plays a critical role in the proliferation of endometrial cancer cells using small interfering RNAs (siRNAs). We identified the prognostically important genes regulated by SETD8 via H4K20 methylation and p53 signaling using chromatin immunoprecipitation sequencing, RNA sequencing, and machine learning. We confirmed that SETD8 expression was elevated in endometrial cancer tissues. Our in vitro results suggest that the suppression of SETD8 using siRNA or a selective inhibitor attenuated cell proliferation and promoted the apoptosis of endometrial cancer cells. In these cells, SETD8 regulates genes via H4K20 methylation and the p53 signaling pathway. We also identified the prognostically important genes related to apoptosis, such as those encoding KIAA1324 and TP73, in endometrial cancer. SETD8 is an important gene for carcinogenesis and progression of endometrial cancer via H4K20 methylation.</jats:p>
収録刊行物
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- Cancers
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Cancers 14 (21), 5367-, 2022-10-31
MDPI AG
