剖析可移植元素和内源性逆转录病毒在线肌肉肉瘤细胞中的HDAC抑制剂的上调:对干扰素反应的影响
Nicolò Gualandi1, Martina Minisini1, Alessio Bertozzo1
1Department of Medicine, Università degli Studi di Udine, P.le Kolbe 4, 33100 Udine, Italy.
Genomics
|August 5, 2024
概括
基斯脱乙酶抑制剂 (HDACIs) 在线肌肉肉瘤细胞中的内源逆转录病毒 (ERVs) 的上调,但令人惊的是没有激活干扰素反应. 增加ERV1的A-to-I编辑可能会影响dsRNA的稳定性,这表明癌症治疗中的HDACI和ADAR联合抑制.
科学领域:
- 癌症生物学 癌症生物学
- 免疫治疗是一种免疫疗法.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 包括内源逆转录病毒 (ERV) 在内的可移植元素 (TE) 在癌症治疗中被研究其免疫调节潜力.
- 试管婴儿可以形成双链RNAs (dsRNAs),激活干扰素反应,这是先天免疫的关键组成部分.
- 基因脱乙酶抑制剂 (HDACIs) 正在探索它们在癌细胞中调节包括TE在内的基因表达的能力.
研究的目的:
- 为了研究不同HDAC抑制剂 (HDACI) 对leiomyosarcoma细胞中TE表达的影响.
- 了解HDACI诱导的TE调节对干扰素反应和潜在治疗策略的影响.
主要方法:
- 用各种针对HDAC1/2/3.3的HDAC抑制剂治疗质肌肉瘤细胞.
- 对内源性逆转录病毒 (ERV) 表达水平的分析.
- 对干扰素反应激活的评估.
- 在ERV1元素中对A-to-I编辑的评估.
- 测量H3K27ac水平和分析相关的基因表达,包括TNFRSF10B等亲细胞突变基因.
主要成果:
- 特定于HDAC1/2/3的抑制剂在leiomyosarcoma细胞中上调了ERVs,特别是ERV1元素.
- 与预期相反,干扰素反应在HDACI治疗后没有被激活.
- 观察到上调ERV1的A-to-I编辑的增加,可能会影响dsRNA的稳定性.
- 在LTR12亚家族中,H3K27ac的水平增加,这表明它在调节前性基因表达中的作用 (例如,TNFRSF10B).
结论:
- HDACIs调节了leiomyosarcoma细胞中的TE表达,并对ERVs进行了特定的上调.
- 对ERV的A-to-I编辑可能是抑制干扰素反应的机制,尽管TE上调.
- 将HDACI与ADAR抑制剂结合起来可能是一个可行的策略,可以诱导癌细胞死亡并增强免疫疗法.
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