ABSTRACT 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.
Huang et al. (2025) studied this question.