转移 RNA 作为癌症进展的动态和关键调节因子。
Transfer RNAs as dynamic and critical regulators of cancer progression.
发表日期:2023 Oct 09
作者:
Alexandra M Pinzaru, Sohail F Tavazoie
来源:
NATURE REVIEWS CANCER
摘要:
转移 RNA (tRNA) 历来被视为将遗传密码解码为蛋白质的非动态接头。最近的工作揭示了这些令人着迷的分子的动态调节作用。 tRNA 检测方法的进步表明,特定的 tRNA 可以根据 DNA 拷贝数和染色质改变进行调节,也可能受到癌细胞或肿瘤微环境中致癌信号和转录调节因子的干扰。特定 tRNA 水平的这种变化已被证明会影响癌症的进展,包括转移。此外,测序方法已经鉴定出 tRNA 衍生的小 RNA,它们影响癌症进展的各个方面,例如细胞增殖和侵袭,并且可以作为各种癌症的诊断和预后生物标志物或假定的治疗靶点。最后,越来越多的证据(包括来自遗传模型的证据)表明,特定的 tRNA 合成酶(负责为 tRNA 添加氨基酸的酶)可以促进或抑制肿瘤形成。在这篇综述中,我们概述了 tRNA 的放松管制如何影响癌症的形成和进展。© 2023。Springer Nature Limited。
Transfer RNAs (tRNAs) have been historically viewed as non-dynamic adaptors that decode the genetic code into proteins. Recent work has uncovered dynamic regulatory roles for these fascinating molecules. Advances in tRNA detection methods have revealed that specific tRNAs can become modulated upon DNA copy number and chromatin alterations and can also be perturbed by oncogenic signalling and transcriptional regulators in cancer cells or the tumour microenvironment. Such alterations in the levels of specific tRNAs have been shown to causally impact cancer progression, including metastasis. Moreover, sequencing methods have identified tRNA-derived small RNAs that influence various aspects of cancer progression, such as cell proliferation and invasion, and could serve as diagnostic and prognostic biomarkers or putative therapeutic targets in various cancers. Finally, there is accumulating evidence, including from genetic models, that specific tRNA synthetases - the enzymes responsible for charging tRNAs with amino acids - can either promote or suppress tumour formation. In this Review, we provide an overview of how deregulation of tRNAs influences cancer formation and progression.© 2023. Springer Nature Limited.