TRF-19-W4PU732S promotes breast cancer cell malignant activity by targeting inhibition of RPL27A (ribosomal protein-L27A)

Abstract

ABSTRACT Breast cancer (BC) is a serious threat to female health. tRNA-derived fragments (tRFs) are popular biomarkers for the diagnosis and treatment of cancer. The purpose of this study was to identify tRFs related to BC and to explore the function and regulatory mechanism of crucial tRFs in BC cells. Small RNA database was used to detect the tRF profiles from BC patients and controls. Differentially expressed tRFs were determined by quantitative reverse transcription PCR (RT-qPCR), and a crucial tRF was evaluated through silence and overexpression experiments, and the target gene was investigated by luciferase reporter gene assay, Western blot and rescue experiment. We screened tRF-19-W4PU732S, which was processed from the mature tRNA-Ser-AGA, and significantly highlyexpressed in BC tissues and cells. Inhibition of tRF-19-W4PU732S weakened MDA-MB-231 cell proliferation, migration and invasion, while enhanced apoptosis. On the contrary, overexpression of tRF-19-W4PU732S promoted MCF-7 cell proliferation, migration and invasion, whereasreduced apoptosis. Furthermore, tRF-19-W4PU732S induced BC cell epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSC) phenotypes, such as up-regulation of OCT-4A, SOX2 and Vimentin and down-regulation of E-cadherin. Ribosomal protein-L27A (RPL27A) was a downstream target of tRF-19-W4PU732S, which was lowly expressed in BC cells. The knockdown of RPL27A expression partially restored the promoting effects of tRF-19-W4PU732S on BC cell viability, invasion, migration, EMT and CSC phenotypes, and the suppression of apoptosis. In conclusion, our results manifested that tRF-19-W4PU732S promotes the malignant activity of BC cells by inhibiting RPL27A, which provides a new scientific basis for the treatment of BC. Abbreviations BC: breast cancer; tRNAs: transfer RNAs; tiRNAs: tRNA-derived stressinduced RNAs; tRFs: tRNA-derived fragments; CCK-8: Cell Counting Kit-8; PI: propidium iodide; EMT: epithelial-to-mesenchymal transition; CSC: cancer stem-like cells; RPL27A: ribosomal protein-L27A; RT-qPCR: quantitative reverse transcription PCR.