Department of General Surgery, Division of gastrointestinal and colorectal Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200205, China.
Department of genecology and obstetrics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200205, China.
Mol Cancer. 2020 Mar 24;19(1):64. doi: 10.1186/s12943-020-01159-9.
Empowered by recent advances of sequencing techniques, transcriptome-wide studies have characterized over 150 different types of post-transcriptional chemical modifications of RNA, ranging from methylations of single base to complex installing reactions catalyzed by coordinated actions of multiple modification enzymes. These modifications have been shown to regulate the function and fate of RNAs and further affecting various cellular events. However, the current understanding of their biological functions in human diseases, especially in cancers, is still limited. Once regarded as "junk" or "noise" of the transcriptome, noncoding RNA (ncRNA) has been proved to be involved in a plethora of cellular signaling pathways especially those regulating cancer initiation and progression. Accumulating evidence has demonstrated that ncRNAs manipulate multiple phenotypes of cancer cells including proliferation, metastasis and chemoresistance and may become promising biomarkers and targets for diagnosis and treatment of cancer. Importantly, recent studies have mapped plenty of modified residues in ncRNA transcripts, indicating the existence of epigenetic modulation of ncRNAs and the potential effects of RNA modulation on cancer progression. In this review, we briefly introduced the characteristics of several main epigenetic marks on ncRNAs and summarized their consecutive effects on cancer cells. We found that ncRNAs could act both as regulators and targets of epigenetic enzymes, which indicated a cross-regulating network in cancer cells and unveil a novel dimension of cancer biology. Moreover, by epitomizing the knowledge of RNA epigenetics, our work may pave the way for the design of patient-tailored therapeutics of cancers.
受测序技术最新进展的推动,转录组范围的研究已经描述了超过 150 种不同类型的 RNA 转录后化学修饰,范围从单个碱基的甲基化到多个修饰酶协同作用催化的复杂安装反应。这些修饰被证明可以调节 RNA 的功能和命运,并进一步影响各种细胞事件。然而,目前对它们在人类疾病中的生物学功能的理解,特别是在癌症中,仍然有限。非编码 RNA(ncRNA)曾经被认为是转录组的“垃圾”或“噪声”,但现已被证明参与了大量的细胞信号通路,特别是那些调节癌症发生和进展的信号通路。越来越多的证据表明,ncRNAs 操纵着包括增殖、转移和化疗耐药性在内的癌细胞的多种表型,并且可能成为癌症诊断和治疗的有前途的生物标志物和靶点。重要的是,最近的研究已经在 ncRNA 转录本中绘制了大量修饰残基,表明 ncRNA 存在表观遗传调控,以及 RNA 调控对癌症进展的潜在影响。在这篇综述中,我们简要介绍了 ncRNA 上几种主要表观遗传标记的特征,并总结了它们对癌细胞的连续影响。我们发现,ncRNA 既可以作为表观遗传酶的调节剂,也可以作为其靶点,这表明癌细胞中存在交叉调控网络,并揭示了癌症生物学的一个新维度。此外,通过总结 RNA 表观遗传学的知识,我们的工作可能为癌症患者定制治疗方法的设计铺平道路。