由JUN诱导的超强增强器RNA形成R循环,促进鼻癌转移
Qunying Jia1, Yuan Tan1, Yuejin Li1
1Hunan Key Laboratory of Oncotarget Gene and Clinical Laboratory, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, 410013, Changsha, China.
Cell death & disease
|July 21, 2023
概括
一种新的超级增强器RNA (seRNA) 通过形成R循环和调节NDRG1.1.等基因来促进鼻癌 (NPC) 转移. 这种seRNA是NPC患者潜在的预后因素.
科学领域:
- 分子瘤学分子瘤学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
背景情况:
- 超级增强剂 (SE) 驱动瘤基因表达,并产生增强剂RNA (eRNA/seRNA),对癌症进展至关重要.
- 鼻癌 (NPC) 转移是一个复杂的过程,受异常基因调节的影响.
研究的目的:
- 识别和表征一种参与NPC转移的新型seRNA.
- 阐明这种seRNA调节目标基因并促进转移的机制.
- 为了评估在NPC患者中识别的seRNA的预后意义.
主要方法:
- 全球运行测序,ChIP测序和RNA测序用于选转移相关的seRNAs.
- 进行了体外和体内功能测试,以评估已识别的seRNA在NPC细胞转移中的作用.
- 机理学研究研究了R循环形成,蛋白相互作用和染色质循环.
主要成果:
- 一种特定的seRNA,seRNA-NPCM,被确定并发现在NPC组织和转移性细胞系中升高.
- JUN转录因子调节了seRNA-NPCM的表达.
- seRNA-NPCM通过形成R循环,招募hnnRNPR和促进染色质循环来激活NDRG1和TRIB1转录来促进NPC细胞转移.
- seRNA-NPCM和NDRG1是NPC患者的独立预后因素.
结论:
- 由JUN介导的seRNA-NPCM是NPC转移的关键驱动因素,通过R循环形成和NDRG1和TRIB1.1的转录调节.
- seRNA-NPCM代表了一个潜在的治疗标,也是鼻癌的宝贵预后生物标志物.
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