A novel 3’tRNA-derived fragment tRF-Val promotes proliferation and inhibits apoptosis by targeting EEF1A1 in gastric cancer

Abstract

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.

Characteristics of tRNA-Derived Small RNAs and microRNAs Associated with Immunocompromise in an Intrauterine Growth-Restricted Pig Model

“…In this study, we find that tRF-5c were the most abundant categories in pig spleen. Previous studies showed that the class of tsRNA in stomach [ 59 ], lung [ 60 ] and plasma [ 61 ] were mainly tRF-5c. However, other results were also reported tiRNAs were primarily observed in ovary [ 62 ] and thyroid [ 63 ].…”

Emerging roles of tRNA-derived fragments in cancer

“…In addition to RNAi abilities, GC-related tRF can also interact with RBPs. Recently, Cui and colleagues identified a 3’-tRF named as tRF-Val as a potential oncogene in GC and confirmed the interaction of tRF-Val with the chaperone molecule EEE1A1 [ 119 ]. They further unraveled that tRF-Val mediated the transport of EEF1A1 to the nucleus, thus improving the interaction of EEF1A1 and MDM2-p53, which resulted in p53 ubiquitination and blockade of p53 signaling pathways [ 119 ].…”

tRFs and tRNA Halves: Novel Cellular Defenders in Multiple Biological Processes

“…In addition, tRNA fragments impact apoptosis. The 3′-tRNA-derived fragment, tRF-Val, inhibits apoptosis by binding to the chaperone molecule, eukaryotic translation elongation factor 1 alpha 1, directly and inhibiting the downstream p53 molecular pathway in gastric cancer [ 109 ]. Furthermore, tRF-315 derived from tRNA-Lys alleviates cisplatin-induced mitochondrial dysfunction and apoptosis in prostate cancer [ 110 ].…”