Huang Shanhe, Li Zonglin, Lin Weilong, Xie Ruihui, Huang Hai
Department of Urology Sun Yat-sen Memorial Hospital, Sun Yat-sen University Guangzhou China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou China.
MedComm (2020). 2025 Aug 3;6(8):e70322. doi: 10.1002/mco2.70322. eCollection 2025 Aug.
RNA epigenetics, also referred to as epitranscriptomics, has emerged as a critical regulatory layer in cancer biology, extending beyond the scope of traditional DNA and histone modifications. It encompasses a series of dynamic posttranscriptional processes-including RNA biosynthesis, splicing, transport, stability, degradation, translation, and chemical modifications-orchestrated by RNA-binding proteins (RBPs) and noncoding RNAs (ncRNAs). Collectively, these mechanisms influence mRNA fate, shape transcriptional output, and reprogram the tumor microenvironment. Importantly, both coding RNA and ncRNA are themselves subjected to epigenetic regulation, forming intricate feedback loops that contribute to oncogenesis, immune evasion, metastasis, and therapeutic resistance. In this review, we systematically synthesize the current understanding of RNA metabolism and RNA epigenetic modifications during tumor progression, with a particular focus on the roles of RBPs and RNA modifications. Furthermore, we highlight recent advances in RNA-based therapeutic strategies, including mRNA vaccines, antisense oligonucleotides, siRNAs, and circRNA scaffolds. These innovative approaches offer promising avenues for targeting transcriptionally active yet genomically "undruggable" cancer drivers. Together, our synthesis provides a comprehensive framework for understanding RNA epigenetics in tumor biology and lays the groundwork for precision oncology guided by transcriptome plasticity.
RNA表观遗传学,也被称为表观转录组学,已成为癌症生物学中的一个关键调控层面,其范围超越了传统的DNA和组蛋白修饰。它涵盖了一系列由RNA结合蛋白(RBP)和非编码RNA(ncRNA)精心编排的动态转录后过程,包括RNA生物合成、剪接、运输、稳定性、降解、翻译和化学修饰。总体而言,这些机制影响mRNA的命运,塑造转录输出,并重新编程肿瘤微环境。重要的是,编码RNA和ncRNA自身也受到表观遗传调控,形成复杂的反馈回路,促进肿瘤发生、免疫逃逸、转移和治疗抗性。在本综述中,我们系统地总结了目前对肿瘤进展过程中RNA代谢和RNA表观遗传修饰的理解,特别关注RBP和RNA修饰的作用。此外,我们强调了基于RNA的治疗策略的最新进展,包括mRNA疫苗、反义寡核苷酸、小干扰RNA(siRNA)和环状RNA支架。这些创新方法为靶向转录活跃但基因组上 “不可成药” 的癌症驱动因素提供了有前景的途径。我们的综述共同提供了一个全面的框架,用于理解肿瘤生物学中的RNA表观遗传学,并为以转录组可塑性为指导的精准肿瘤学奠定基础。