tRNA-derived fragment tRF-03357 promotes cell proliferation, migration and invasion in high-grade serous ovarian cancer

Onco Targets Ther. 2019 Aug 16:12:6371-6383. doi: 10.2147/OTT.S206861. eCollection 2019.

Abstract

Background: High-grade serous ovarian cancer (HGSOC) is one of the most common ovarian epithelial malignancies. tRNA-derived fragments (tRFs) have been identified as novel potential biomarkers and targets for cancer therapy. Nevertheless, the influence of tRFs on HGSOC remains unknown. This study aimed to identify HGSOC-associated tRFs and to investigate the function and mechanism of key tRFs in SK-OV-3 ovarian cancer cells.

Methods: The tRF profiles in HGSOC patients and controls were investigated using small RNA sequencing. Differentially expressed tRFs were verified by real-time PCR, and a key tRF was evaluated in a function study.

Results: A total of 27 tRFs were differentially expressed between HGSOC patients and controls. Differentially expressed tRFs were mainly involved in the functions of protein phosphorylation, transcription and cell migration and the pathway of cancer, and the MAPK and Wnt signaling pathways. Real-time PCR verified that tRF-03357 and tRF-03358 were significantly increased in the HGSOC serum samples and SK-OV-3 cells compared to their expression levels in the controls. Importantly, tRF-03357 promoted SK-OV-3 cell proliferation, migration and invasion. Moreover, tRF-03357 was predictively targeted, and significantly downregulated HMBOX1.

Conclusion: This study suggests that tRF-03357 might promote cell proliferation, migration and invasion, partly by modulating HMBOX1 in HGSOC.

Keywords: cell growth; high-grade serous ovarian cancer; invasion; migration; tRNA-derived fragments.