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生物标志物RIPK3在黑色素瘤和表观遗传编辑中通过高甲基化被静止,恢复了其瘤抑制功能

Sarah Arroyo Villora¹, Paula Castellanos Silva¹, Tamara Zenz¹

¹Institute for Genetics, Justus-Liebig-University Giessen, 35390 Giessen, Germany.

|February 24, 2024

概括

受体相互作用的氨酸/氨酸蛋白激酶3 (RIPK3) 在黑色素瘤中起到瘤抑制作用. 通过高甲基化进行表观遗传失活化与瘤进展相关,但基于CRISPR的脱甲基化恢复了RIPK3的表达,并降低了黑色素瘤细胞的适应性.

科学领域:

癌症生物学癌症生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
黑色素瘤研究黑色素瘤研究

背景情况:

癌症仍然是全球主要的死亡原因,像DNA高甲基化这样的表观遗传修饰通过非激活瘤抑制基因,有助于瘤发生.
基因促进体附近的CpG岛屿的高甲基化显著影响基因表达,在癌症发育中发挥关键作用.

研究的目的:

在黑色素瘤中研究潜在的瘤抑制基因受体相互作用氨酸/氨酸蛋白激酶3 (RIPK3) 的表观遗传调节和失活.
探索RIPK3表观遗传沉默的功能后果及其作为生物标记物的潜力.

主要方法:

双硫酸盐热序测试用于检测和量化黑色素瘤样本中的RIPK3 CpG岛屿高甲基化.
基于CRISPR/dCas9的表观遗传编辑系统 (CRISPRa激活) 用于调节RIPK3 DNA甲基化和表达.
黑色素瘤细胞的表型表征使用光显微镜,流动细胞计和伤口愈合试验进行.

主要成果:

在RIPK3 CpG岛屿高甲基化和在黑色素瘤中减少RIPK3表达之间观察到显著的相关性.
随着瘤的进展,RIPK3的甲基化率增加,这表明它与黑色素瘤的进展有关.
由表观遗传编辑诱导的RIPK3再表达和去甲基化导致黑色素瘤细胞适应性降低,并证明其瘤抑制功能.

结论:

在黑色素瘤中,RIPK3作为一种表观遗传调节的瘤抑制剂起作用.
RIPK3表观遗传状态可以作为黑色素瘤分类和进展的潜在生物标志物.
准RIPK3表观遗传失活化为黑色素瘤提供了潜在的治疗策略.

关键词:

克里斯普尔-Cas9是什么意思通过DNA (超) 甲基化.在RIPK3中使用RIPK3.生物标志物生物标志物癌症癌症癌症癌症癌症已经停用dCas9的dCas9 编辑表观遗传学编辑皮肤皮肤黑色素瘤瘤抑制基因的基因抑制器

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