向SUMO2可以逆转SS18::SSX融合基蛋白驱动的异常表观遗传重新连接,并损害肉瘤生成
Rema Iyer1, Anagha Deshpande1, Aditi Pedgaonkar1
1Cancer Genome and Epigenetics Program, National Cancer Institute-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
研究人员确定了小型无类修饰剂2 (SUMO2) 作为突肉瘤 (SySa) 的关键依赖. 抑制SUMO2有效地向SySa细胞,为这种侵袭性癌症提供了一个有前途的新治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 突肉瘤 (SySa) 是一种由SS18::SSX融合蛋白驱动的侵袭性软组织癌症.
- 对针对SySa.Sa的向治疗非常需要.
研究的目的:
- 为了识别对SySa细胞适应性有必要的选择性基因.
- 探索针对已识别的漏洞的治疗潜力.
主要方法:
- 挖掘癌症依赖性地图数据用于Sysa选择性基因.
- 进行了有针对性的CRISPR库选.
- 通过使用TAK-981.1,利用SUMO2抑制.
- 进行了转录基因分析和表观遗传分析.
主要成果:
- 小型泛素类修饰剂2 (SUMO2) 被确定为SySa.中的关键依赖性.
- 抑制SUMO2在体外和体内强烈抑制了SySa细胞的生长.
- SUMO2 抑制逆转了SS18::SSX驱动的基因表达程序.
- 向SUMO2降低了SS18::SSX蛋白水平和H2AK119ub表观遗传标记.
结论:
- SUMO2 是突肉瘤中一种新的和选择性的脆弱性.
- 向SUMO2为软组织瘤提供了一个有前途的治疗策略.
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