Zhang Yi, Li Lvyuan, Mendoza Juana Jessica, Wang Dan, Yan Qijia, Shi Lei, Gong Zhaojian, Zeng Zhaoyang, Chen Pan, Xiong Wei
NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, China.
Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medicine Sciences, Central South University, Changsha, Hunan, 410078, China.
Mol Cancer. 2024 Dec 27;23(1):280. doi: 10.1186/s12943-024-02194-6.
RNA modifications are widespread throughout the mammalian transcriptome and play pivotal roles in regulating various cellular processes. These modifications are strongly linked to the development of many cancers. One of the most prevalent forms of RNA modifications in humans is adenosine-to-inosine (A-to-I) editing, catalyzed by the enzyme adenosine deaminase acting on RNA (ADAR) in double-stranded RNA (dsRNA). With advancements in RNA sequencing technologies, the role of A-to-I modification in cancer has garnered increasing attention. Research indicates that the levels and specific sites of A-to-I editing are significantly altered in many malignant tumors, correlating closely with tumor progression. This editing occurs in both coding and noncoding regions of RNA, influencing signaling pathways involved in cancer development. These modifications can either promote or suppress cancer progression through several mechanisms, including inducing non-synonymous amino acid mutations, altering the immunogenicity of dsRNAs, modulating mRNA interactions with microRNAs (miRNAs), and affecting the splicing of circular RNAs (circRNAs) as well as the function of long non-coding RNAs (lncRNAs). A comprehensive understanding of A-to-I RNA editing is crucial for advancing the diagnosis, treatment, and prognosis of human cancers. This review explores the regulatory mechanisms of A-to-I editing in cancers and examines their potential clinical applications. It also summarizes current research, identifies future directions, and highlights potential therapeutic implications.
RNA修饰广泛存在于哺乳动物转录组中，并在调节各种细胞过程中发挥关键作用。这些修饰与许多癌症的发生发展密切相关。人类中最普遍的RNA修饰形式之一是腺苷到肌苷（A-to-I）编辑，它由双链RNA（dsRNA）中的RNA腺苷脱氨酶（ADAR）催化。随着RNA测序技术的进步，A-to-I修饰在癌症中的作用越来越受到关注。研究表明，在许多恶性肿瘤中，A-to-I编辑的水平和特定位点发生了显著改变，与肿瘤进展密切相关。这种编辑发生在RNA的编码区和非编码区，影响癌症发展所涉及的信号通路。这些修饰可以通过多种机制促进或抑制癌症进展，包括诱导非同义氨基酸突变、改变dsRNA的免疫原性、调节mRNA与微小RNA（miRNA）的相互作用，以及影响环状RNA（circRNA）的剪接和长链非编码RNA（lncRNA）的功能。全面了解A-to-I RNA编辑对于推进人类癌症的诊断、治疗和预后至关重要。本综述探讨了癌症中A-to-I编辑的调控机制，并研究了其潜在的临床应用。它还总结了当前的研究，确定了未来的方向，并强调了潜在的治疗意义。
