研究动态
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TRDMT1介导的RNA C-5甲基化作为新型抗癌治疗的靶点。

TRDMT1-mediated RNA C-5 methylation as a novel target in anticancer therapy.

发表日期:2023 Aug 23
作者: Anna Lewinska, Jagoda Adamczyk-Grochala, Maciej Wnuk
来源: BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

摘要:

影响RNA修饰的景观在不同癌细胞中经常被观察到,这与癌细胞表型特征的发展如持续增殖、迁移和侵袭、抗凋亡和代谢重编程有关。DNMT2/TRDMT1甲基转移酶,最初被归类为DNA甲基转移酶,可以甲基化tRNA和mRNA,促进tRNA稳定和正确的蛋白质合成,并组织DNA损伤应答(DDR)和DNA稳定性。TRDMT1与癌症进展有关,因为其水平可以升高,在多种癌症类型中可以观察到其突变。TRDMT1基因敲除(KO)可以增加对放射治疗和化学治疗的不同来源的癌细胞的敏感性。本综述论文基于文献数据描述了TRDMT1在不同生物系统中的生理和病理生理学作用,重点是人类正常和癌细胞。还介绍和评估了TRDMT1的潜在底物、抑制剂和催化活性和细胞定位的调控机制。提出并讨论了TRDMT1作为抗癌治疗中一个有前景的新靶点。版权所有 © 2023。Elsevier B.V.出版。
Affected landscape of RNA modifications is frequently observed in different cancer cells that can be associated with the development of cancer cell phenotypic traits such as sustained proliferation, migration and invasion, apoptosis resistance and metabolic reprograming. DNMT2/TRDMT1 5-methylcytosine methyltransferase, initially classified as DNA methyltransferase, can methylate both tRNA and mRNA promoting tRNA stability and proper protein synthesis, and orchestrating DNA damage response (DDR) and DNA stability, respectively. TRDMT1 is associated with cancer progression as its levels can be elevated and its mutations can be observed in a number of cancer types. TRDMT1 gene knockout (KO) can sensitize cancer cells of different origin to radiotherapy and chemotherapy. In the present review paper, based on literature data, the physiological and pathophysiological roles of TRDMT1 in different biological systems are described with the emphasis on human normal and cancer cells. Potential TRDMT1 substrates, inhibitors and regulatory mechanisms of catalytic activity and cellular localization are also presented and evaluated. TRDMT1 as a novel promising target in anticancer therapy is proposed and discussed.Copyright © 2023. Published by Elsevier B.V.