The biological behavior of tRNA-derived fragment tRF-Leu-AAG in pancreatic cancer cells.

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.

Low expression of tRF-Pro-CGG predicts poor prognosis in pancreatic ductal adenocarcinoma.

BACKGROUND & AIMS: tRFs (tRNA-derived RNA fragments) have been reported to facilitate cancer progression in multiple cancers. However, their role in pancreatic ductal adenocarcinoma (PDAC) remains to be determined. In this study, we mainly investigated the expression of tRF-Pro-CGG in pancreatic ductal adenocarcinoma and evaluated its relationship with the clinicopathology and survival time of patients. METHODS: 37 cases of pancreatic ductal adenocarcinoma, and 15 cases of normal pancreatic tissues were collected which were resected by surgery from January 2017 to June 2020 from the Department of Hepatobiliary and Pancreatic surgery of Changzhou second people's Hospital. The expression of tRF-Pro-CGG in paraffin-embedded tissues was detected by fluorescence in situ hybridization (FISH). The clinical data including age, sex, tumor location, tumor diameter, tumor clinical stage (TNM stage), depth of invasion, regional lymph node metastasis, serum CA199, and serum CEA were collected and analyzed retrospectively, whether the expression tRF-Pro-CGG was correlation with the pathological parameters and clinical outcomes of patients. RESULTS: The expression level of tRF-Pro-CGG was significantly downregulated in PDAC and associated with an advanced TNM stage (P=0.000) and the N stage (P=0.000) of patients. More importantly, low tRF-Pro-CGG expression predicted poor survival in PDAC patients (P=0.003). CONCLUSIONS: TRF-Pro-CGG is under-expressed in PDAC and is associated with short clinical survival and poor prognosis. tRF-Pro-CGG is an independent prognostic factor, which highlights its role as a potential biomarker for PDAC progression and therapy.