Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, 21983, South Korea.
Institute for Artificial Intelligence and Biomedical Research, Medicinal Bioconvergence Research Center, College of Pharmacy and College of Medicine, Gangnam Severance Hospital, Yonsei University, Incheon, 21983, South Korea.
Exp Mol Med. 2022 May;54(5):553-566. doi: 10.1038/s12276-022-00765-5. Epub 2022 May 2.
Although key tumorigenic and tumor-suppressive factors have been unveiled over the last several decades, cancer remains the most life-threatening disease. Multiomic analyses of patient samples and an in-depth understanding of tumorigenic processes have rapidly revealed unexpected pathologic associations of new cellular factors previously overlooked in cancer biology. In this regard, the newly discovered activities of human aminoacyl-tRNA synthases (ARSs) deserve attention not only for their pathological significance in tumorigenesis but also regarding diagnostic and therapeutic implications. ARSs are not only essential enzymes covalently linking substrate amino acids to cognate tRNAs for protein synthesis but also function as regulators of cellular processes by sensing different cellular conditions. With their catalytic role in protein synthesis and their regulatory role in homeostasis, functional alterations or dysregulation of ARSs might be pathologically associated with tumorigenesis. This review focuses on the potential implications of ARS genes and proteins in different aspects of cancer based on various bioinformatic analyses and experimental data. We also review their diverse activities involving extracellular secretion, protein-protein interactions, and amino acid sensing, which are related to cancers. The newly discovered cancer-related activities of ARSs are expected to provide new opportunities for detecting, preventing and curing cancers.
尽管在过去几十年中已经揭示了一些关键的致癌和抑癌因素，但癌症仍然是最致命的疾病。对患者样本的多组学分析和对致癌过程的深入了解，迅速揭示了以前在癌症生物学中被忽视的新细胞因子的意外病理关联。在这方面，新发现的人类氨酰-tRNA 合成酶（ARS）的活性不仅因其在肿瘤发生中的病理意义，而且因其诊断和治疗意义而值得关注。ARS 不仅是将底物氨基酸共价连接到用于蛋白质合成的同源 tRNA 的必需酶，而且还通过感知不同的细胞条件来作为细胞过程的调节剂。由于 ARS 在蛋白质合成中的催化作用及其在动态平衡中的调节作用，ARS 的功能改变或失调可能与肿瘤发生病理性相关。本综述基于各种生物信息学分析和实验数据，重点讨论了 ARS 基因和蛋白质在癌症不同方面的潜在意义。我们还回顾了它们涉及细胞外分泌、蛋白质-蛋白质相互作用和氨基酸感应的各种活性，这些活性与癌症有关。ARS 的新发现的与癌症相关的活性有望为癌症的检测、预防和治疗提供新的机会。
