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

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.

SNORA71A Promotes Colorectal Cancer Cell Proliferation, Migration, and Invasion.

Small nucleolar RNAs (snoRNAs) play a crucial role during colorectal cancer (CRC) development. The study of SNORA71A is few, and its role in CRC is unknown. This study focused on screening abnormal snoRNAs in CRC and exploring the role of key snoRNA in CRC. The expression pattern of snoRNAs in 3 CRC and 3 normal colon tissues was detected via small RNA sequencing. The six candidate snoRNAs were identified by quantitative PCR (qPCR). Subsequently, the expression level of SNORA71A was further verified through the Cancer Genome Atlas (TCGA) data analysis and qPCR. The CCK8 and transwell assays were used to detect the functional role of SNORA71A in CRC cells. The integrated analysis of snoRNA expression profile indicated that a total 107 snoRNAs were significantly differentially expressed (DE) in CRC tissues compared with normal tissues, including 45 upregulated and 62 downregulated snoRNAs. Bioinformatics analysis revealed that the DE snoRNAs were mainly implicated in "detection of chemical stimulus involved in sensory perception of smell" and "sensory perception of smell" in the biological process. The DE snoRNAs were preferentially enriched in "olfactory transduction" and "glycosphingolipid biosynthesis-ganglio series pathway." The expression of SNORA71A was upregulated in CRC tissues and cells. SNORA71A expression showed statistically significant correlations with TNM stage (P = 0.0196) and lymph node metastasis (P = 0.0189) and can serve as biomarkers for CRC. Importantly, SNORA71A significantly facilitated the CRC cell proliferation, migration, and invasion. Our findings indicate that SNORA71A screened by sequencing acted as an oncogene and promoted proliferation, migration, and invasion ability of CRC cells.