Low G9a expression is a tumor progression factor of colorectal cancer via IL-8 promotion. (30th May 2022)

• Record Type: Journal Article
• Authors: Ichikawa, Yoshitoshi; Takahashi, Hidekazu; Chinen, Yoshinao; Arita, Asami; Sekido, Yuki; Hata, Tsuyoshi; Ogino, Takayuki; Miyoshi, Norikatsu; Uemura, Mamoru; Yamamoto, Hirofumi; Mizushima, Tsunekazu; Doki, Yuichiro; Eguchi, Hidetoshi
• Is Part Of: Carcinogenesis. Volume 43:Number 8(2022)
• Page Start: 797
• Page End: 807
• Publication Date: 2022-05-30
• Subjects: Carcinogenesis -- Periodicals; Cancer -- Genetic aspects -- Periodicals; Cancer -- Prevention -- Periodicals; Cancer -- Periodicals; 616.994071
• DOI: 10.1093/carcin/bgac050
• Languages: English
• ISSNs: 0143-3334

Abstract

Abstract: 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. Abstract : G9a suppresses IL-8 expression in colorectal cancer cells and is a significant independent prognostic factor for colorectal cancer. Graphical Abstract: