Xu Qingling, Jia Yi, Liu Ying, Wu Bing, Wang Jianxun, Ao Xiang, Ding Wei
Department of Comprehensive Internal Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
School of Basic Medicine, Qingdao University, Qingdao, Shandong, China.
Front Oncol. 2025 May 19;15:1554888. doi: 10.3389/fonc.2025.1554888. eCollection 2025.
Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) generated through the reverse splicing of mRNA precursors (pre-mRNAs). They possess a unique loop structure and exhibit remarkable stability. CircRNAs have emerged as promising biomarkers for cancer, with specific circRNAs playing crucial roles in cancer drug discovery, treatment, and resistance mechanisms. N6 methyl adenosine (m6A) represents the most prevalent RNA modification in eukaryotes. In 2017, researchers identified that m6A modifications also occur in circRNAs, displaying unique characteristics. m6A-modified circRNAs undergo reversible regulation mediated by enzymes involved in m6A modification pathways. These modified circRNAs interact with m6A-binding proteins, thereby influencing processes such as alternative splicing, translation and degradation. Some circRNAs enhance their metabolism or facilitate nuclear export to the cytoplasm by interacting with enzymes involved in m6A regulation. The study of m6A-modified circRNAs has gained great attention in circRNA research due to their association with various diseases. This review summarizes the functional mechanisms of circRNAs regulated by m6A modifications and their implications in cancer occurrence and therapy, with a primary focus on the genesis, regulatory mechanisms, and functional roles of m6A-modified circRNAs in the biology of diverse types of cancers. Additionally, we explore the potential application of m6A-modified circRNAs in clinical cancer treatment.
环状RNA（circRNAs）是一类通过mRNA前体（pre-mRNAs）的反向剪接产生的非编码RNA（ncRNAs）。它们具有独特的环状结构，并且表现出显著的稳定性。CircRNAs已成为有前景的癌症生物标志物，特定的circRNAs在癌症药物发现、治疗及耐药机制中发挥着关键作用。N6甲基腺苷（m6A）是真核生物中最普遍的RNA修饰。2017年，研究人员发现m6A修饰也存在于circRNAs中，并呈现出独特的特征。m6A修饰的circRNAs经历由m6A修饰途径中涉及的酶介导的可逆调控。这些修饰的circRNAs与m6A结合蛋白相互作用，从而影响可变剪接、翻译和降解等过程。一些circRNAs通过与参与m6A调控的酶相互作用来增强其代谢或促进向细胞质的核输出。由于m6A修饰的circRNAs与多种疾病相关，它们的研究在circRNA研究中受到了极大关注。本综述总结了由m6A修饰调控的circRNAs的功能机制及其在癌症发生和治疗中的意义，主要关注m6A修饰的circRNAs在不同类型癌症生物学中的起源、调控机制和功能作用。此外，我们还探讨了m6A修饰的circRNAs在临床癌症治疗中的潜在应用。
