Low G9a expression is a tumor progression factor of colorectal cancer via IL-8 promotion
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- Yoshitoshi Ichikawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
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- Hidekazu Takahashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
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- Yoshinao Chinen
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
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- Asami Arita
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
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- Yuki Sekido
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
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- Tsuyoshi Hata
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
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- Takayuki Ogino
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
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- Norikatsu Miyoshi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
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- Mamoru Uemura
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
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- Hirofumi Yamamoto
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
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- Tsunekazu Mizushima
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
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- Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
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- Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , Suita, Osaka , Japan
Description
<jats:title>Abstract</jats:title> <jats:p>The histone methyltransferase G9a is expressed in various types of cancer cells, including colorectal cancer (CRC) cells. Interleukin 8 (IL)-8, also known as C-X-C motif chemokine ligand 8 (CXCL8), is a chemokine that plays a pleiotropic function in the regulation of inflammatory responses and cancer development. Here, we examined the relationship between G9a and IL-8 and the clinical relevance of this association. We immunohistochemically analyzed 235 resected CRC samples to correlate clinical features. Samples with high G9a expression had better overall survival and relapse-free survival than those with low G9a expression. Univariate and multivariate analyses demonstrated that low G9a expression remained a significant independent prognostic factor for increased disease recurrence and decreased survival (P < 0.05). G9a was expressed at high levels in commercially available CRC cell lines HCT116 and HT29. Knockdown of G9a by siRNA, shRNA or the G9a-specific inhibitor BIX01294 upregulated IL-8 expression. The number of spheroids was significantly increased in HCT116 cells with stably suppressed G9a expression, and the number of spheroids was significantly decreased in HCT116 cells with stably suppressed IL-8 expression. Thus, the suppression of IL-8 by G9a may result in a better prognosis in CRC cases with high G9a expression. Furthermore, G9a may suppress cancer stemness and increase chemosensitivity by controlling IL-8. Therefore, G9a is a potential novel marker for predicting CRC prognosis, and therapeutic targeting of G9a in CRC should be controversial.</jats:p>
Journal
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- Carcinogenesis
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Carcinogenesis 43 (8), 797-807, 2022-05-30
Oxford University Press (OUP)
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Details 詳細情報について
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- CRID
- 1360298757186502528
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- ISSN
- 14602180
- 01433334
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- Data Source
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- Crossref
- KAKEN