Department of Anesthesiology and Critical Care, Elias Clinical Emergency Hospital, 011461 Bucharest, Romania.
Department of Neurosurgery, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania.
Int J Mol Sci. 2021 Jan 8;22(2):581. doi: 10.3390/ijms22020581.
Currently, for seemingly every type of cancer, dysregulated levels of non-coding RNAs (ncRNAs) are reported and non-coding transcripts are expected to be the next class of diagnostic and therapeutic tools in oncology. Recently, alterations to the ncRNAs transcriptome have emerged as a novel hallmark of cancer. Historically, ncRNAs were characterized mainly as regulators and little attention was paid to the mechanisms that regulate them. The role of modifications, which can control the function of ncRNAs post-transcriptionally, only recently began to emerge. Typically, these modifications can be divided into reversible (i.e., chemical modifications: mC, hmC, mA, mA, and pseudouridine) and non-reversible (i.e., editing: ADAR dependent, APOBEC dependent and ADAR/APOBEC independent). The first research papers showed that levels of these modifications are altered in cancer and can be part of the tumorigenic process. Hence, the aim of this review paper is to describe the most common regulatory modifications (editing and chemical modifications) of the traditionally considered "non-functional" ncRNAs (i.e., microRNAs, long non-coding RNAs and circular RNAs) in the context of malignant disease. We consider that only by understanding this extra regulatory layer is it possible to translate the knowledge about ncRNAs and their modifications into clinical practice.
目前,似乎每种类型的癌症都报道了非编码 RNA(ncRNA)水平的失调,并且预计非编码转录本将成为肿瘤学中下一类诊断和治疗工具。最近,ncRNA 转录组的改变已成为癌症的一个新标志。从历史上看,ncRNA 主要被表征为调节剂,而很少关注调节它们的机制。最近才开始出现可以控制 ncRNA 转录后功能的修饰的作用。通常,这些修饰可以分为可逆的(即化学修饰:mC、hmC、mA、mG 和假尿嘧啶)和不可逆的(即编辑:ADAR 依赖性、APOBEC 依赖性和 ADAR/APOBEC 独立性)。第一篇研究论文表明,这些修饰的水平在癌症中发生改变,并且可以成为肿瘤发生过程的一部分。因此,本文综述的目的是描述传统上被认为“非功能性”的 ncRNA(即 microRNA、长非编码 RNA 和环状 RNA)在恶性疾病背景下最常见的调节修饰(编辑和化学修饰)。我们认为,只有通过了解这一额外的调节层,才有可能将 ncRNA 及其修饰的知识转化为临床实践。