胰腺癌（PAAD）是一种危及生命的癌症。探索新的诊断和治疗靶点有助于改善其预后。 tRNA 衍生的小非编码 RNA (tsRNA) 是一种新型的基因表达调节因子，其失调与许多人类癌症密切相关。然而 tsRNA 在 PAAD 中的表达和功能尚不清楚。我们的研究使用 RNA 测序来鉴定在无葡萄糖或高葡萄糖培养基中培养的 PAAD 细胞中的 tsRNA 表达谱，发现 tRF-18-8R6546D2 是一种未表征的 tsRNA，在 PAAD 细胞和组织中具有显着高表达。临床上，tRF-18-8R6546D2 与 PAAD 患者预后不良有关，可用于将其与健康人群区分开来。在功能上，在体外和体内，tRF-18-8R6546D2过表达促进PAAD细胞增殖、迁移和侵袭，抑制细胞凋亡，而tRF-18-8R6546D2敲低则表现出相反的作用。从机制上讲，tRF-18-8R6546D2部分通过直接沉默ASCL2并进一步调节其下游基因如MYC和CASP3来促进PAAD恶性。这些发现表明 tRF-18-8R6546D2 是一种新型致癌因子，可以成为 PAAD 的有前途的诊断或预后生物标志物和治疗靶标。版权所有 © 2024。由 Elsevier B.V. 出版。

Pancreatic adenocarcinoma (PAAD) is a life-threatening cancer. Exploring new diagnosis and treatment targets helps improve its prognosis. tRNA-derived small non-coding RNAs (tsRNAs) are a novel type of gene expression regulators and their dysregulation is closely related to many human cancers. Yet the expression and functions of tsRNAs in PAAD are not well understood. Our study used RNA sequencing to identify tsRNA expression profiles in PAAD cells cultured in no or high glucose media and found tRF-18-8R6546D2 was an uncharacterized tsRNA, which has significantly high expression in PAAD cells and tissues. Clinically, tRF-18-8R6546D2 is linked to poor prognosis in PAAD patients and can be used to distinguish them from healthy populations. Functionally, in vitro and vivo, tRF-18-8R6546D2 over-expression promoted PAAD cell proliferation, migration and invasion, inhibited apoptosis, whereas tRF-18-8R6546D2 knock-down showed opposite effects. Mechanistically, tRF-18-8R6546D2 promoted PAAD malignancy partly by directly silencing ASCL2 and further regulating its downstream genes such as MYC and CASP3. These findings show that tRF-18-8R6546D2 is a novel oncogenic factor and can be a promising diagnostic or prognostic biomarker and therapeutic target for PAAD.Copyright © 2024. Published by Elsevier B.V.