tRF-34-P4R8YP9LON4VHM Promotes Hepatocellular Carcinoma Progression and Tumour Cell-Induced Angiogenesis via the MEK/ERK Pathway.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and poses a significant global health challenge. In recent years, tRNA-derived small RNAs (tsRNAs) have gained significant attention due to their potential role in various cancers, including HCC. In this study, we reported that tRF-34-P4R8YP9LON4VHM expression was elevated in HCC tissues and cell lines. The association between tRF-34-P4R8YP9LON4VHM expression and HCC patients' clinicopathological parameters was determined using tissue microarrays of 90 patients, and we found that it was positively associated with the level of AFP, tumour size, microvascular density (MVD), and TNM stage. We performed CCK8, colony formation assay, EdU, cell cycle analysis, transwell assay, and tube formation assay to verify that tRF-34-P4R8YP9LON4VHM could enhance HCC proliferation, migration, invasion, and tumour cell-induced angiogenesis in vitro and in vivo. Mechanistically, tRF-34-P4R8YP9LON4VHM could downregulate DAB2IP expression by directly targeting its 3'-UTR, consequently activating the MEK/ERK signalling pathway and promoting the secretion of VEGFA from HCC cells into the supernatant. In conclusion, our research indicated that tRF-34-P4R8YP9LON4VHM might act as a crucial player in molecular mechanisms and provide novel treatment strategies for HCC patients.