通过内源转录诱导病毒模拟,DNA脱甲基剂向结肠直肠癌细胞
David Roulois1, Helen Loo Yau2, Rajat Singhania1
1Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Cell
|August 29, 2015
概括
低剂量的5-AZA-CdR通过诱导病毒模拟作用来向结直肠癌发病细胞 (CICs). 这激活了MDA5/MAVS/IRF7通路,为结直肠癌提供了新的治疗策略.
科学领域:
- 癌症学
- 分子生物学
- 免疫学
背景情况:
- 通过不清楚的机制显示抗瘤作用的DNA脱甲基剂.
- 结肠直肠癌启动细胞 (CIC) 对瘤生长和复发至关重要.
研究的目的:
- 阐明低剂量5-AZA-CdR在结直肠癌中的作用机制.
- 研究病毒模拟和RNA识别途径在5-AZA-CdR疗效中的作用.
主要方法:
- 在结直肠癌细胞中的实验和生物信息分析.
- 研究了5-AZA-CdR对CIC,dsRNA诱导和MDA5/MAVS/IRF7通路的影响.
- 关键路径组件 (MDA5,MAVS,IRF7) 的破坏和dSRNA转染实验.
主要成果:
- 低剂量的5-AZA-CdR诱导了结直肠CIC中的病毒模拟.
- 这涉及从内源逆转录病毒元素产生dSRNA,激活MDA5/MAVS/IRF7通路.
- 干扰这种途径取消了5-AZA-CdR对CIC的向和长期增长抑制.
结论:
- 脱甲基化剂的抗瘤机制包括诱导病毒模拟和激活MDA5/MAVS/IRF7通路.
- 这一途径对5-AZA-CdR对结直肠CIC的疗效至关重要.
- MDA5/MAVS/IRF7通路是结直肠癌治疗的潜在治疗点.
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