Kurkowiak Małgorzata, Arcimowicz Łukasz, Chruściel Elżbieta, Urban-Wójciuk Zuzanna, Papak Ines, Keegan Liam, O'Connell Mary, Kowalski Jacek, Hupp Ted, Marek-Trzonkowska Natalia
International Centre for Cancer Vaccine Science (ICCVS), University of Gdańsk, Gdańsk, Poland.
CEITEC Masaryk University, Brno, CZ, Czech Republic.
RNA Biol. 2021 Nov;18(11):1524-1539. doi: 10.1080/15476286.2021.1877024. Epub 2021 Feb 17.
RNA editing is one of the most prevalent and abundant forms of post-transcriptional RNA modification observed in normal physiological processes and often aberrant in diseases including cancer. RNA editing changes the sequences of mRNAs, making them different from the source DNA sequence. Edited mRNAs can produce editing-recoded protein isoforms that are functionally different from the corresponding genome-encoded protein isoforms. The major type of RNA editing in mammals occurs by enzymatic deamination of adenosine to inosine (A-to-I) within double-stranded RNAs (dsRNAs) or hairpins in pre-mRNA transcripts. Enzymes that catalyse these processes belong to the adenosine deaminase acting on RNA (ADAR) family. The vast majority of knowledge on the RNA editing landscape relevant to human disease has been acquired using cancer cell culture models. The limitation of such models, however, is that the physiological or disease relevance of results obtained is not necessarily obvious. In this review we focus on discussing occurring RNA editing events that have been identified in human cancer tissue using samples surgically resected or clinically retrieved from patients. We discuss how RNA editing events occurring in tumours can identify pathological signalling mechanisms relevant to human cancer physiology which is linked to the different stages of cancer progression including initiation, promotion, survival, proliferation, immune escape and metastasis.
RNA编辑是在正常生理过程中观察到的最普遍且丰富的转录后RNA修饰形式之一,在包括癌症在内的疾病中常常出现异常。RNA编辑会改变mRNA的序列,使其与源DNA序列不同。经过编辑的mRNA可以产生与相应基因组编码的蛋白质异构体功能不同的编辑重编码蛋白质异构体。哺乳动物中主要的RNA编辑类型是通过双链RNA(dsRNA)或前体mRNA转录本中的发夹结构内的腺苷酶促脱氨为肌苷(A到I)而发生的。催化这些过程的酶属于作用于RNA的腺苷脱氨酶(ADAR)家族。关于与人类疾病相关的RNA编辑情况的绝大多数知识都是使用癌细胞培养模型获得的。然而,此类模型的局限性在于所获得结果的生理或疾病相关性不一定明显。在本综述中,我们重点讨论使用手术切除的样本或从患者临床获取的样本在人类癌症组织中鉴定出的正在发生的RNA编辑事件。我们讨论肿瘤中发生的RNA编辑事件如何能够识别与人类癌症生理学相关的病理信号传导机制,这与癌症进展的不同阶段相关,包括起始、促进、存活、增殖、免疫逃逸和转移。