在miRNA种子中广泛存在的8-oxoguanine修改差异性调节了氧化还原依赖癌症的发展
Sangkyeong Eom1, Jongjin Peak1, Jongyeun Park1
1Department of Life Sciences, Korea University, Seoul, Korea.
Nature cell biology
|September 11, 2023
概括
氧化应激通过8-oxoguanine (o8G) 修改微RNA (miRNA),影响癌症. 在miRNA中特定的o8G位置可以抑制或促进瘤,提供新的治疗点.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 史诗转录组学 史诗转录组学
背景情况:
- 氧化应激是癌症发展的已知因素,影响基因表达.
- 8-oxoguanine (o8G) 是一种氧化修饰物,可以改变RNA结构和相互作用.
- 在微RNA (miRNA) 中o8G的特定调节作用及其对癌症的影响仍然在很大程度上是未知的.
研究的目的:
- 调查瘤微RNA中特定位置的8-oxoguanine修饰的发生和功能意义.
- 确定这些o8G修饰在特定癌症类型中的临床相关性.
- 探索调节o8G在微RNA中的治疗潜力,用于癌症治疗.
主要方法:
- 在测序数据中分析o8G诱导的关氨酸-氨酸 (o8G>T) 变化,以确定瘤miRNAs中的o8G位置.
- 在质瘤和肝癌模型中验证特定的o8G修饰miRNA的功能作用.
- 在肝癌小鼠模型中研究miR-122的逐步氧化及其调制.
主要成果:
- 在瘤miRNA中发现了广泛的,位置特定的o8G,特别是在5'种子区域.
- 这些o8G修饰在临床上与低级质瘤和肝肝细胞癌有关.
- 针对miR-124和let-7的特定o8G修改抑制了结质瘤,而针对miR-122和let-7的o8G促进了肝癌的进展.
- 观察到miR-122的逐步氧化,其调节减少了小鼠肝癌的发展.
结论:
- 经氧化应激重编程的microRNAs的EPITranscriptional 8-oxoguanine修饰在癌症中起着至关重要的作用.
- o8G修饰的位置和模式决定了miRNA是否抑制或促进瘤进展.
- 针对microRNA中的o8G修饰,为新型癌症疗法提供了一个有希望的途径.
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