Chen Meiling, Chen Yuanzhong, Wang Kitty, Deng Xiaolan, Chen Jianjun
Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China.
Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, California, USA.
Clin Transl Med. 2024 Jun;14(6):e1666. doi: 10.1002/ctm2.1666.
Dysregulated RNA modifications, stemming from the aberrant expression and/or malfunction of RNA modification regulators operating through various pathways, play pivotal roles in driving the progression of haematological malignancies. Among RNA modifications, N-methyladenosine (mA) RNA modification, the most abundant internal mRNA modification, stands out as the most extensively studied modification. This prominence underscores the crucial role of the layer of epitranscriptomic regulation in controlling haematopoietic cell fate and therefore the development of haematological malignancies. Additionally, other RNA modifications (non-mA RNA modifications) have gained increasing attention for their essential roles in haematological malignancies. Although the roles of the mA modification machinery in haematopoietic malignancies have been well reviewed thus far, such reviews are lacking for non-mA RNA modifications. In this review, we mainly focus on the roles and implications of non-mA RNA modifications, including N-acetylcytidine, pseudouridylation, 5-methylcytosine, adenosine to inosine editing, 2'-O-methylation, N-methyladenosine and N-methylguanosine in haematopoietic malignancies. We summarise the regulatory enzymes and cellular functions of non-mA RNA modifications, followed by the discussions of the recent studies on the biological roles and underlying mechanisms of non-mA RNA modifications in haematological malignancies. We also highlight the potential of therapeutically targeting dysregulated non-mA modifiers in blood cancer.
RNA修饰失调源于通过各种途径发挥作用的RNA修饰调节因子的异常表达和/或功能障碍，在推动血液系统恶性肿瘤的进展中起关键作用。在RNA修饰中，N-甲基腺苷（m⁶A）RNA修饰作为最丰富的内部mRNA修饰，是研究最广泛的修饰。这种突出地位凸显了表观转录组调控层在控制造血细胞命运以及血液系统恶性肿瘤发展中的关键作用。此外，其他RNA修饰（非m⁶A RNA修饰）因其在血液系统恶性肿瘤中的重要作用而受到越来越多的关注。尽管到目前为止，m⁶A修饰机制在造血系统恶性肿瘤中的作用已有很好的综述，但非m⁶A RNA修饰的此类综述却很缺乏。在本综述中，我们主要关注非m⁶A RNA修饰的作用和影响，包括N-乙酰胞苷、假尿苷化、5-甲基胞嘧啶、腺苷到肌苷的编辑、2'-O-甲基化、N-甲基腺苷和N-甲基鸟苷在造血系统恶性肿瘤中的作用。我们总结了非m⁶A RNA修饰的调节酶和细胞功能，随后讨论了非m⁶A RNA修饰在血液系统恶性肿瘤中的生物学作用和潜在机制的最新研究。我们还强调了靶向血液癌症中失调的非m⁶A修饰因子进行治疗的潜力。
