转移 RNA 衍生片段 (tRF) 是一类小的非编码调节 RNA，参与许多疾病的病理生理学。然而，tRF 在癌症进展中的作用在很大程度上仍然难以捉摸。在这里，我们证明了泛癌 3'-tRF，CAT1（癌症相关 tRF 1）在肿瘤中普遍上调，并与包括肺癌在内的多种癌症的不良预后相关。癌细胞中上调的 CAT1 通过多重剪接 (RBPMS) 与 RNA 结合蛋白结合，并取代 RBPMS 中的 NOTCH2 关联，从而抑制随后的 CCR4-NOT 去腺苷化复合物介导的 NOTCH2 mRNA 衰减。 CAT1 增强的 NOTCH2 表达可促进肺癌细胞在体外和体内的增殖和转移。此外，与非癌症对照受试者相比，肺癌患者的血浆 CAT1 水平显着升高。我们的研究结果揭示了癌症特异性上调 CAT1 与癌症进展之间的内在联系，显示了 3'-tRF 对癌症中 NOTCH 信号传导的调节，并强调了其巨大的临床潜力。版权所有 © 2023 作者。由爱思唯尔公司出版。保留所有权利。

Transfer RNA-derived fragments (tRFs) are a class of small non-coding regulatory RNAs that are involved in the pathophysiology of many diseases. However, the role of tRFs in cancer progression remains largely elusive. Here, we demonstrate that a pan-cancer 3'-tRF, CAT1 (cancer associated tRF 1), is ubiquitously upregulated in tumors and associated with poor prognosis of a variety of cancers, including lung cancer. The upregulated CAT1 in cancer cells binds to RNA-binding protein with multiple splicing (RBPMS) and displaces NOTCH2 association from RBPMS, thereby inhibiting the subsequent CCR4-NOT deadenylation-complex-mediated NOTCH2 mRNA decay. The CAT1-enhanced NOTCH2 expression promotes lung cancer cell proliferation and metastasis in vitro and in vivo. In addition, plasma CAT1 levels are substantially increased in patients with lung cancer compared to non-cancer control subjects. Our findings reveal an intrinsic connection between cancer-specific upregulation of CAT1 and cancer progression, show the regulation of NOTCH signaling in cancer by a 3'-tRF, and highlight its great clinical potential.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.