中南大学湘雅医学院附属肿瘤医院(湖南省肿瘤医院)乳腺肿瘤整形外科,长沙 410013
国家自然科学基金(82203448),湖南省自然科学基金(2025JJ40072),广东省基础与应用基础研究基金(2023A1515010624)和广州市基础与应用基础研究专题市校(院)联合资助项目(2023A03J0413)资助。
Department of Breast Oncoplastic Surgery, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China
This work was supported by grants from The National Natural Science Foundation of China (82203448), the Hunan Provincial Natural Science Foundation of China (2025JJ40072), the GuangDong Basic and Applied Basic Research Foundation (2023A1515010624), and the Guangzhou Basic and Applied Basic Research Foundation (2023A03J0413).
环状RNA(circular RNA,circRNA)是来源于前体mRNA的一类环状结构RNA,其形成依赖于反向剪接。由于缺乏典型的5′端帽结构与3′端多聚腺苷酸尾,circRNA在细胞中不易受到外切酶降解,从而具有比线性RNA更高的稳定性。长期以来,circRNA被视为非编码分子,但近年来的研究不断显示,部分circRNA能够在特定条件下被翻译成多肽或蛋白质。当前已识别的翻译方式主要包括依赖内部核糖体进入位点(IRES)的非依赖5′端帽结构的翻译,以及由N6-甲基腺苷(m6A)修饰介导的启动机制,这些进展促使我们重新审视非编码RNA的功能边界。越来越多的证据表明,circRNA编码的多肽通过介导肿瘤相关信号通路调控及蛋白质相互作用网络,参与肿瘤发生发展中的关键生物学过程,既可能增强肿瘤细胞的增殖、迁移、侵袭和上皮–间质转化,也可能通过抑制信号通路或干扰蛋白质相互作用发挥抑癌作用。因此,这类多肽在肿瘤发生与发展的多个阶段扮演了复杂而重要的角色。本文围绕circRNA的翻译机制进行系统性综述,重点总结其编码的多肽在肿瘤细胞行为调控中的具体功能,并进一步分析其作为潜在诊断标志物和治疗靶点的应用前景。明确circRNA翻译产物的生物学意义,将为阐明肿瘤发生机制和开发新的精准医学策略提供重要启示。
Circular RNAs (circRNAs) represent a distinct group of RNA molecules produced through back-splicing of precursor mRNAs. Their covalently closed structure, which lacks both a 5′ cap and a poly(A) tail, renders them highly resistant to exonucleolytic degradation and contributes to their remarkable intracellular stability. Although circRNAs were historically viewed as noncoding transcripts, accumulating evidence indicates that certain circRNAs can undergo translation under appropriate molecular contexts. Two major modes of noncanonical translation have been described so far: initiation mediated by internal ribosome entry sites (IRESs) and translation triggered by N6-methyladenosine (m6A) modification. Recent studies have revealed that, beyond their canonical classification as non-coding RNAs, circRNAs can give rise to functional peptides through cap-independent translational mechanisms. Accumulating evidence indicates that circRNA-encoded peptides participate in key biological processes during tumor initiation and progression by modulating tumor-associated signaling pathways and protein-protein interaction networks. Functionally, these peptides may promote tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition, while others exert tumor-suppressive effects by inhibiting oncogenic signaling pathways or interfering with critical protein interactions. Their dual and context-dependent functions highlight the complexity of circRNA-mediated regulation and suggest that these translation products participate in multiple layers of tumor initiation and progression. In this review, we synthesize current knowledge regarding the molecular mechanisms that enable circRNAs to be translated, with particular attention to IRES-driven initiation, m6A-dependent regulation, ribosome accessibility, and the structural determinants required for translation competence. We further summarize well-characterized circRNA-encoded peptides and discuss how they influence tumor-associated signaling networks. In addition, we examine the potential translational applications of these peptides, including their value as diagnostic indicators, prognostic markers, or therapeutic entry points. Their inherent sequence stability, relative expression specificity, and detectability in clinical specimens make circRNA-derived peptides promising candidates for future biomarker and therapeutic development. Overall, circRNA translation research is reshaping our understanding of RNA function and offers new perspectives for studying tumor biology. We propose that expanding investigations into circRNA-encoded peptides will not only improve the mechanistic resolution of cancer research but may also pave the way for innovative strategies in precision oncology, including RNA-based therapeutics and peptide-targeting interventions.
向琼,杨丽嫦,李赞,凌云.环状RNA翻译机制及其编码多肽在肿瘤发生与调控中的作用[J].生物化学与生物物理进展,2026,53(2):356-368
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