Identification of a novel tRNA-derived small RNA fragment, tRF-16-2YU04DE, with the potential of inhibiting endometrial cancer progression.

As the second most prevalent gynecological malignancy, the incidence and mortality of endometrial cancer (EC) are rising. Transfer RNA-derived small RNAs (tsRNAs), a novel class of non-coding RNAs, are frequently dysregulated in multiple cancers. Nevertheless, its precise roles in EC remain to be elucidated. High-throughput sequencing technology was employed to characterize the expression profiles of tsRNAs in EC and healthy controls (HCs) tissues, followed by differential expression analyses. Quantitative real-time polymerase chain reaction (RT-qPCR) was applied to identify the target tsRNA for further biological functions experiments. Bioinformatics followed with RT-qPCR and Western blot systematically explore potential target genes and delineated the underlying molecular mechanisms. Eventually, a total of 284 tsRNAs were identified in both EC and HC tissues with 26 upregulated and 47 downregulated significantly. tRF-16-2YU04DE was finally identified as the target molecule. Functional experiments revealed that the overexpression of tRF-16-2YU04DE not only inhibited the proliferation, migration, and invasion of EC cells, but also promoted apoptosis and disrupted cell cycle progression. Although the downregulation of tRF-16-2YU04DE significantly promotes the proliferation, migration, and invasion of EC cells, it does not have a notable effect on cell apoptosis or the cell cycle. Bioinformatics analyses combined with RT-qPCR and Western blot results showed KLF5 expression was particularly downregulated by the overexpression of tRF-16-2YU04DE. tRF-16-2YU04DE-inhibiting EC progression in vitro may serve as a promising therapeutic target. The underlying mechanism is likely linked to its RNA silencing function, specifically targeting the 3' untranslated region (3' -UTR) of KLF5 mRNA.