Epitranscriptomics and cervical cancer: the emerging role of m6A, m5C and m1A RNA modifications.

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Akshat D Modi, Hira Zahid, Ashlyn Chase Southerland, Dharmeshkumar M Modi
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引用次数: 0

Abstract

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 N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A), 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.

表转录组学与宫颈癌:m6A、m5C 和 m1A RNA 修饰的新作用。
宫颈癌(CC)是发病率最高、危害最大的妇科癌症之一,它通过基因和表观遗传学的改变,导致致癌活性增强和肿瘤抑制机制失调。尽管医疗技术不断进步,但由于复发率高和对现有治疗方法的耐药性,晚期患者的预后仍然极差。因此,寻找潜在的预后生物标志物的工作被提上日程,以揭示 CC 发病的新模式并开发新型抗癌疗法。表观转录组修饰(可逆的表观遗传 RNA 修饰)通过决定 RNA 的命运和介导 RNA 的相互作用来调控各种生物过程。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(尤其是N6-甲基腺苷(m6A)、5-甲基胞嘧啶(m5C)和N1-甲基腺苷(m1A))在调控CC的发生、发展和转移过程中的细胞和分子作用。我们深入探讨了 50 多种 RNA 在调控 CC 的肿瘤发生、增殖、迁移、侵袭、存活、自噬、干性、上皮-间质转化、代谢(葡萄糖、脂质、谷氨酸和谷氨酰胺)、抗药性(药物和辐射)、血管生成和复发方面的表观转录组学机制。此外,我们还简要概述了针对CC中内源性RNA编辑蛋白表达的改变以及编码和非编码RNA上RNA修饰的异常沉积的治疗潜力。
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来源期刊
Expert Reviews in Molecular Medicine
Expert Reviews in Molecular Medicine BIOCHEMISTRY & MOLECULAR BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
7.40
自引率
1.60%
发文量
45
期刊介绍: Expert Reviews in Molecular Medicine is an innovative online journal featuring authoritative and timely Reviews covering gene therapy, immunotherapeutics, drug design, vaccines, genetic testing, pathogenesis, microbiology, genomics, molecular epidemiology and diagnostic techniques. We especially welcome reviews on translational aspects of molecular medicine, particularly those related to the application of new understanding of the molecular basis of disease to experimental medicine and clinical practice.
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