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通过CRISPR/dCAS9-介导的DNA脱甲基化屏幕识别了结直肠癌的功能表观遗传决定因素
Juan Ramón Tejedor1,2,3,4, Alfonso Peñarroya1,2, Javier Gancedo-Verdejo1,2,3,4
1Nanomaterials and Nanotechnology Research Center (CINN), Spanish National Research Council (CSIC), 33940, El Entrego, Asturias, Spain.
Clinical epigenetics
|August 23, 2023
概括
DNA甲基化可能驱动结肠直肠癌 (CRC) 的发展. RSPO2的表观遗传重新激活导致癌细胞增殖受损,这表明针对CRC中的DNA甲基化具有治疗潜力.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
- 基因组学就是基因组学.
背景情况:
- 瘤抑制基因的促剂高甲基化在恶性转变期间在结直肠癌 (CRC) 中很常见.
- 这种表观遗传机制在癌症中的功能作用与致癌的后果是不清楚的.
研究的目的:
- 研究DNA甲基化对结直肠癌中的基因表达和细胞增殖的功能影响.
- 通过对瘤抑制基因的表观遗传重新激活来识别潜在的治疗点.
主要方法:
- 人类CRC样本和细胞系的综合性多原子分析.
- CRISPR-Cas9表观基因组编辑工具 (dCas9-TET1,dCas9-TET-IM) 和一个gRNA库来调节56个CRC链接促进者的DNA甲基化.
- 高含量细胞增殖查以评估功能后果.
主要成果:
- 大多数测试区域的表观遗传调制对基因表达和癌细胞活力产生了轻微影响.
- 在p53缺乏的CRC细胞系中,RSPO2的表观遗传活性显著损害了增殖.
- RSPO2表观遗传沉默发生在从腺瘤发展为癌症的中后期事件中.
结论:
- 基因甲基化在结直肠癌中发挥着潜在的驱动作用.
- 这些发现为针对CRC中瘤抑制基因的表观遗传重新激活的新疗法开辟了道路.
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