Cancer Institute, Affiliated People's Hospital of Jiangsu University, No 8, Dianli Road, Zhenjiang, Jiangsu Province, 212002, People's Republic of China.
Department of Gastroenterology, The Suqian Clinical College of Xuzhou Medical University, No 120, Suzhi Road, Suqian, Jiangsu Province, 223812, People's Republic of China.
Mol Cancer. 2024 Oct 18;23(1):232. doi: 10.1186/s12943-024-02148-y.
R-loops are three-stranded nucleic acid structures composed of an RNA-DNA hybrid and a displaced DNA strand. They are widespread and play crucial roles in regulating gene expression, DNA replication, and DNA and histone modifications. However, their regulatory mechanisms remain unclear. As R-loop detection technology advances, changes in R-loop levels have been observed in cancer models, often associated with transcription-replication conflicts and genomic instability. N6-methyladenosine (m6A) is an RNA epigenetic modification that regulates gene expression by affecting RNA localization, splicing, translation, and degradation. Upon reviewing the literature, we found that R-loops with m6A modifications are implicated in tumor development and progression. This article summarizes the molecular mechanisms and detection methods of R-loops and m6A modifications in gene regulation, and reviews recent research on m6A-modified R-loops in oncology. Our goal is to provide new insights into the origins of genomic instability in cancer and potential strategies for targeted therapy.
R 环是由 RNA-DNA 杂合体和一条链位移的 DNA 组成的三链核酸结构。它们广泛存在，在调节基因表达、DNA 复制以及 DNA 和组蛋白修饰方面发挥着关键作用。然而，其调控机制尚不清楚。随着 R 环检测技术的发展，在癌症模型中观察到 R 环水平的变化，这通常与转录-复制冲突和基因组不稳定性有关。N6-甲基腺苷（m6A）是一种 RNA 表观遗传修饰，通过影响 RNA 定位、剪接、翻译和降解来调节基因表达。在查阅文献后，我们发现 m6A 修饰的 R 环与肿瘤的发生和发展有关。本文总结了 R 环和 m6A 修饰在基因调控中的分子机制和检测方法，并综述了近年来肿瘤学中 m6A 修饰的 R 环的研究进展。我们的目标是为癌症中基因组不稳定性的起源以及靶向治疗的潜在策略提供新的见解。
