PDF(Pubmed)
Abstract：
Pancreatic cancer (PC) is a life-threatening cancer with increasing incidence in developed countries. Reports indicate that tRNA-derived fragments (tRFs) are possible therapeutic targets and biomarkers for cancer treatment. Nonetheless, the effect of tRF-Leu-AAG on PC is unclear. This study aims to explore the role of tRF-Leu-AAG and upstream frameshift mutant 1 (UPF1) in the development of PC and its potential underlying mechanisms. High-throughput second-generation sequencing techniques were used to detect the expression of tRFs in cancerous and adjacent normal tissues from PC patients. The role of tRF-Leu-AAG proliferation in PC cells was investigated via the Cell Counting Kit-8 (CCK8) assay. The effect of tRF-Leu-AAG on the invasion and migration ability of PC cells was also determined by the transwell assay. Thereafter, the downstream target genes of tRF-Leu-AAG were comprehensively predicted using bioinformatics analysis databases. We also used the Dual-Luciferase Reporter assay to assess the nexus between tRF-Leu-AAG and UPF1. Eventually, Western Blot was used to validate the expression of UPF1 in PC cells. A total of 33 tRF expressions significantly varied from PC patients. RT-qPCR confirmed that the expression of tRF-Leu-AAG was observably up-regulated in PC cells as compared to the control cells. Importantly, knockdown of tRF-Leu-AAG observably inhibited cell proliferation, migration, and invasion. Furthermore, according to the predicted frameshift database results, the UPF1 acted as downstream target genes for tRF-Leu-AAG and significantly down-regulated UPF1 expression.
摘要：
胰腺癌（PC）是一种威胁生命的癌症，在发达国家发病率越来越高。报告表明，tRNA衍生片段（tRF）可能是癌症治疗的治疗靶标和生物标志物。尽管如此，tRF-Leu-AAG对PC的影响尚不清楚。本研究旨在探讨tRF-Leu-AAG和上游移码突变体1（UPF1）在PC发育中的作用及其潜在的潜在机制。高通量第二代测序技术用于检测来自PC患者的癌组织和邻近正常组织中tRFs的表达。通过细胞计数试剂盒-8(CCK8)测定研究了tRF-Leu-AAG在PC细胞中增殖的作用。tRF-Leu-AAG对PC细胞侵袭和迁移能力的影响也通过transwell测定来确定。此后,使用生物信息学分析数据库对tRF-Leu-AAG的下游靶基因进行综合预测。我们还使用双荧光素酶报告基因测定来评估tRF-Leu-AAG和UPF1之间的联系。最终,Western印迹用于验证UPF1在PC细胞中的表达。PC患者共有33个tRF表达显着不同。RT-qPCR证实,与对照细胞相比,tRF-Leu-AAG的表达在PC细胞中被观察到上调。重要的是,tRF-Leu-AAG敲低可观察到抑制细胞增殖，迁移,和入侵。此外，根据预测的框架迁移数据库结果，UPF1充当tRF-Leu-AAG的下游靶基因，并显着下调UPF1的表达。
