DNA methylome and transcriptome alterations and cancer prevention by curcumin in colitis-accelerated colon cancer in mice

被引：95

作者：

Guo, Yue ^{[1
,2
]}

Wu, Renyi ^{[2
]}

Gaspar, John M. ^{[2
]}

Sargsyan, Davit ^{[2
]}

Su, Zheng-Yuan ^{[2
,3
]}

Zhang, Chengyue ^{[1
,2
]}

Gao, Linbo ^{[2
]}

Cheng, David ^{[2
]}

Li, Wenji ^{[2
]}

Wang, Chao ^{[2
]}

Yin, Ran ^{[2
]}

Fang, Mingzhu ^{[4
]}

Verzi, Michael P. ^{[5
]}

Hart, Ronald P. ^{[6
]}

Kong, Ah-Ng ^{[2
]}

机构：

[1] Rutgers State Univ, Grad Program Pharmaceut Sci, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USA

[2] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmaceut, Room 228,160 Frelinghuysen Rd, Piscataway, NJ 08854 USA

[3] Chung Yuan Christian Univ, Dept Biosci Technol, Taoyuan 32023, Taiwan

[4] Rutgers State Univ, Environm & Occupat Hlth Sci Inst, Piscataway, NJ 08854 USA

[5] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA

[6] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA

来源：

CARCINOGENESIS | 2018年 / 39卷 / 05期

关键词：

TUMOR-NECROSIS-FACTOR; INFLAMMATORY CYTOKINES CXCL1; GENOME-WIDE ANALYSIS; COLORECTAL-CANCER; METHYLATION PROFILES; ULCERATIVE-COLITIS; OXIDATIVE STRESS; FACTOR-ALPHA; EXPRESSION; CELLS;

D O I：

10.1093/carcin/bgy043

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms could play an important role in the initiation and progression of colon cancer. Curcumin, a dietary phytochemical, shows promising effects in suppressing colitis-associated colon cancer in azoxymethane-dextran sulfate sodium (AOM-DSS) mice. However, the potential epigenetic mechanisms of curcumin in colon cancer remain unknown. In this study, the anticancer effect of curcumin in suppressing colon cancer in an 18-week AOM-DSS colon cancer mouse model was confirmed. We identified lists of differentially expressed and differentially methylated genes in pairwise comparisons and several pathways involved in the potential anticancer effect of curcumin. These pathways include LPS/IL-1-mediated inhibition of RXR function, Nrf2-mediated oxidative stress response, production of NO and ROS in macrophages and IL-6 signaling. Among these genes, Tnf stood out with decreased DNA CpG methylation of Tnf in the AOM-DSS group and reversal of the AOM-DSS induced Tnf demethylation by curcumin. These observations in Tnf methylation correlated with increased and decreased Tnf expression in RNA-seq. The functional role of DNA methylation of Tnf was further confirmed by in vitro luciferase transcriptional activity assay. In addition, the DNA methylation level in a group of inflammatory genes was decreased in the AOM+DSS group but restored by curcumin and was validated by pyrosequencing. This study shows for the first time epigenomic changes in DNA CpG methylation in the inflammatory response from colitis-associated colon cancer and the reversal of their CpG methylation changes by curcumin. Future clinical epigenetic studies with curcumin in inflammation-associated colon cancer would be warranted.

引用

页码：669 / 680

页数：12

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