At present, it is commonly believed that tRFs and tiRNAs are formed by the specific and selective shear of tRNAs under certain pressure stimulation, rather than by random degradation of tRNA. tRFs and tiRNAs have been reported to contribute to the biological process of a variety of human cancers. However, the evidence for the mechanisms of tRFs and tiRNAs in the occurrence and development of gastric cancer (GC) is still insufficient. Here, we aimed to explore the carcinogenic roles of tRFs and tiRNAs in GC with RNA-sequencing technique, and found a novel 3’tRNA-derived fragment tRF-Val was significantly upregulated in GC tissues and cell lines. tRF-Val expression was positively correlated with tumor size and the depth of tumor invasion in GC tissues. Functionally, tRF-Val promoted proliferation and invasion, and inhibited apoptosis in GC cells. Mechanistically, tRF-Val directly bound to the chaperone molecule EEF1A1, mediated its transport into the nucleus and promoted its interaction with MDM2 (a specific p53 E3 ubiquitin ligase), thus inhibiting the downstream molecular pathway of p53 and promoting GC progression. These findings provided a new potential therapeutic target for GC and a new explanation for the occurrence of GC.
As oncogenes and tumor suppressor genes, long non-coding RNAs (lncRNAs) regulate the biological behavior of gastric cancer (GC) cells such as proliferation, invasion, and metastasis through various signal pathways. At present, although numerous lncRNAs that significantly influence the development and progression of GC have been identified, a considerable number of them have not been found and studied yet. In this study, we identified a new lncRNA derived from pseudogenes WFDC21P, which have not been reported in any previous GC study. LncRNA WFDC21P was significantly upregulated in GC cells and tissues, and clinically associated with the pathological stages of advanced GC. WFDC21P promoted proliferation and metastasis of GC cells both in vitro and in vivo. LncRNA WFDC21P was directly bound to GTPase Ran and it promoted the activity of the Akt/GSK3β/β-catenin pathway. Forkhead Box P3 (FOXP3), as a transcription factor of WFDC21P, was directly bound to the promoter region and it positively regulated the transcription of WFDC21P. This finding may provide a novel biomarker and therapeutic target for GC.
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