Department of Biological Sciences, University of Toronto, Scarborough, Canada.
Department of Biology, University of Toronto, Mississauga, Canada.
Expert Rev Mol Med. 2024 Oct 8;26:e20. doi: 10.1017/erm.2024.20.
Cervical cancer (CC), one of the most prevalent and detrimental gynaecologic cancers, evolves through genetic and epigenetic alterations resulting in the promotion of oncogenic activity and dysfunction of tumour-suppressing mechanisms. Despite medical advancement, the prognosis for advanced-stage patients remains extremely low due to high recurrence rates and resistance to existing treatments. Thereby, the search for potential prognostic biomarkers is heightened to unravel new modalities of CC pathogenesis and to develop novel anti-cancer therapies. Epitranscriptomic modifications, reversible epigenetic RNA modifications, regulate various biological processes by deciding RNA fate to mediating RNA interactions. This narrative review provides insight into the cellular and molecular roles of endogenous RNA-editing proteins and their associated epitranscriptomic modifications, especially -methyladenosine (mA), 5-methylcytosine (mC) and -methyladenosine (mA), in governing the development, progression and metastasis of CC. We discussed the in-depth epitranscriptomic mechanisms underlying the regulation of over 50 RNAs responsible for tumorigenesis, proliferation, migration, invasion, survival, autophagy, stemness, epithelial-mesenchymal transition, metabolism (glucose, lipid, glutamate and glutamine), resistance (drug and radiation), angiogenesis and recurrence of CC. Additionally, we provided a concise overview of the therapeutic potential of targeting the altered expression of endogenous RNA-editing proteins and aberrant deposition of RNA modifications on both coding and non-coding RNAs in CC.
宫颈癌 (CC) 是最常见和危害最大的妇科癌症之一，其发生是由于遗传和表观遗传改变导致致癌活性的促进和肿瘤抑制机制的功能障碍。尽管医学取得了进步，但由于高复发率和对现有治疗方法的耐药性，晚期患者的预后仍然极低。因此，寻找潜在的预后生物标志物的需求增加，以揭示 CC 发病机制的新方式，并开发新的抗癌疗法。
表观转录组修饰是可逆的 RNA 表观遗传修饰，通过决定 RNA 命运来调节 RNA 相互作用，从而调节各种生物学过程。本综述深入探讨了内源性 RNA 编辑蛋白及其相关表观转录组修饰（特别是 mA、mC 和 mA）在调节 CC 发生、发展和转移中的细胞和分子作用。我们讨论了 50 多种负责肿瘤发生、增殖、迁移、侵袭、存活、自噬、干性、上皮-间充质转化、代谢（葡萄糖、脂质、谷氨酸和谷氨酰胺）、耐药性（药物和辐射）、血管生成和 CC 复发的 RNA 调节的深入表观转录组机制。此外，我们还简要概述了靶向内源性 RNA 编辑蛋白表达改变和 RNA 修饰在编码和非编码 RNA 上的异常沉积在 CC 中的治疗潜力。
