从分子发病机制到治疗:解析人类癌症中非编码 RNA/DNMT3A 轴。
From molecular pathogenesis to therapy: Unraveling non-coding RNAs/DNMT3A axis in human cancers.
机构信息
School of Medicine, Nantong University, Nantong 226001, China.
Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
出版信息
Biochem Pharmacol. 2024 Apr;222:116107. doi: 10.1016/j.bcp.2024.116107. Epub 2024 Mar 2.
Cancer is a comprehensive classification encompassing more than 100 forms of malignancies that manifest in diverse tissues within the human body. Recent studies have provided evidence that aberrant epigenetic modifications are pivotal indicators of cancer. Epigenetics encapsulates DNA methyltransferases as a crucial class of modifiers. DNMTs, including DNMT3A, assume central roles in DNA methylation processes that orchestrate normal biological functions, such as gene transcription, predominantly in mammals. Typically, deviations in DNMT3A function engender distortions in factors that drive tumor growth and progression, thereby exacerbating the malignant phenotype of tumors. Consequently, such abnormalities pose significant challenges in cancer therapy because they impede treatment efficacy. Non-coding RNAs (ncRNAs) represent a group of RNA molecules that cannot encode functional proteins. Recent investigation attests to the crucial significance of regulatory ncRNAs in epigenetic regulation. Notably, recent reports have illuminated the complex interplay between ncRNA expression and epigenetic regulatory machinery, including DNMT3A, particularly in cancer. Recent findings have demonstrated that miRNAs, namely miR-770-5p, miR-101, and miR-145 exhibit the capability to target DNMT3A directly, and their aberration is implicated in diverse cellular abnormalities that predispose to cancer development. This review aims to articulate the interplay between DNMT3A and the ncRNAs, focusing on its impact on the development and progression of cancer, cancer therapy resistance, cancer stem cells, and prognosis. Importantly, the emergence of such reports that suggest a connection between DNMT3A and ncRNAs in several cancers indicates that this connecting axis offers a valuable target with significant therapeutic potential that might be exploited for cancer management.
癌症是一种综合性的分类,涵盖了 100 多种恶性肿瘤,这些肿瘤在人体的不同组织中表现出来。最近的研究表明,异常的表观遗传修饰是癌症的重要指标。表观遗传学包括 DNA 甲基转移酶作为一类重要的修饰物。DNMTs,包括 DNMT3A,在 DNA 甲基化过程中发挥核心作用,这些过程协调正常的生物功能,如基因转录,主要在哺乳动物中。通常,DNMT3A 功能的偏差会导致驱动肿瘤生长和进展的因素发生扭曲,从而加剧肿瘤的恶性表型。因此,这些异常在癌症治疗中构成了重大挑战,因为它们阻碍了治疗效果。非编码 RNA(ncRNA)是一组不能编码功能蛋白的 RNA 分子。最近的研究证明了调节性 ncRNA 在表观遗传调控中的关键意义。值得注意的是,最近的报告揭示了 ncRNA 表达与表观遗传调节机制(包括 DNMT3A)之间的复杂相互作用,特别是在癌症中。最近的发现表明,miRNAs,即 miR-770-5p、miR-101 和 miR-145,能够直接靶向 DNMT3A,它们的异常与导致癌症发展的多种细胞异常有关。本综述旨在阐述 DNMT3A 与 ncRNA 之间的相互作用,重点讨论其对癌症的发生和发展、癌症治疗耐药性、癌症干细胞和预后的影响。重要的是,这些表明 DNMT3A 和 ncRNA 在几种癌症中存在联系的报告的出现表明,这种连接轴提供了一个具有重要治疗潜力的有价值的靶点,可能被用于癌症管理。