Pinello Natalia, Sun Stephanie, Wong Justin Jong-Leong
Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia.
Sydney Medical School, The University of Sydney, Camperdown 2050, Australia.
Cancer Biol Med. 2018 Nov;15(4):323-334. doi: 10.20892/j.issn.2095-3941.2018.0365.
N-methyladenosine (mA) is an essential RNA modification that regulates key cellular processes, including stem cell renewal, cellular differentiation, and response to DNA damage. Unsurprisingly, aberrant mA methylation has been implicated in the development and maintenance of diverse human cancers. Altered mA levels affect RNA processing, mRNA degradation, and translation of mRNAs into proteins, thereby disrupting gene expression regulation and promoting tumorigenesis. Recent studies have reported that the abnormal expression of mA regulatory enzymes affects mA abundance and consequently dysregulates the expression of tumor suppressor genes and oncogenes, including , , , and . In this review, we discuss the specific roles of mA "writers", "erasers", and "readers" in normal physiology and how their altered expression promotes tumorigenesis. We also describe the potential of exploiting the aberrant expression of these enzymes for cancer diagnosis, prognosis, and the development of novel therapies.
N6-甲基腺苷(m6A)是一种重要的RNA修饰,可调节关键的细胞过程,包括干细胞更新、细胞分化以及对DNA损伤的反应。不出所料,异常的m6A甲基化与多种人类癌症的发生和维持有关。m6A水平的改变会影响RNA加工、mRNA降解以及mRNA翻译成蛋白质的过程,从而破坏基因表达调控并促进肿瘤发生。最近的研究报道,m6A调节酶的异常表达会影响m6A丰度,进而失调肿瘤抑制基因和癌基因的表达,包括[此处列举的基因未给出具体名称,无法准确翻译]。在本综述中,我们讨论了m6A“书写器”“擦除器”和“阅读器”在正常生理中的具体作用,以及它们表达的改变如何促进肿瘤发生。我们还描述了利用这些酶的异常表达进行癌症诊断、预后评估以及开发新疗法的潜力。