Journal Article

The role of tRF-Val-CAC-010 in lung adenocarcinoma: implications for tumorigenesis and metastasis

Luo, Li-Lin, Wang, Li, Cao, Yue, Zhang, Juan-Juan, Xie, Yu-Xin, Li, Linhui, Long, Zheng-Bo, Wang, Wan-Pu, Yang, Hui

2024

Overview

Objective Transfer RNA-derived fragments (tRFs) are short non-coding RNA (ncRNA) sequences, ranging from 14 to 30 nucleotides, produced through the precise cleavage of precursor and mature tRNAs. While tRFs have been implicated in various diseases, including cancer, their role in lung adenocarcinoma (LUAD) remains underexplored. This study aims to investigate the impact of tRF-Val-CAC-010, a specific tRF molecule, on the phenotype of LUAD cells and its role in tumorigenesis and progression in vivo. Methods The expression level of tRF-Val-CAC-010 was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Specific inhibitors and mimics of tRF-Val-CAC-010 were synthesized for transient transfection. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8), while cell invasion and migration were evaluated through Transwell invasion and scratch assays. Flow cytometry was utilized to analyze cell cycle and apoptosis. The in vivo effects of tRF-Val-CAC-010 on tumor growth and metastasis were determined through tumor formation and metastasis imaging experiments in nude mice. Results The expression level of tRF-Val-CAC-010 was upregulated in A549 and PC9 LUAD cells ( P  < 0.01). Suppression of tRF-Val-CAC-010 expression resulted in decreased proliferation of A549 and PC9 cells ( P  < 0.001), reduced invasion and migration of A549 ( P  < 0.05, P  < 0.001) and PC9 cells ( P  < 0.05, P  < 0.01), enhanced apoptosis in both A549 ( P  < 0.05) and PC9 cells ( P  < 0.05), and increased G2 phase cell cycle arrest in A549 cells ( P  < 0.05). In vivo, the tumor formation volume in the tRF-inhibitor group was significantly smaller than that in the model and tRF-NC groups ( P  < 0.05). The metastatic tumor flux value in the tRF-inhibitor group was also significantly lower than that in the model and tRF-NC groups ( P  < 0.05). Conclusion This study demonstrates that tRF-Val-CAC-010 promotes proliferation, migration, and invasion of LUAD cells and induces apoptosis in vitro, however, its specific effects on the cell cycle require further elucidation. Additionally, tRF-Val-CAC-010 enhances tumor formation and metastasis in vivo. Therefore, tRF-Val-CAC-010 may serve as a novel diagnostic biomarker and potential therapeutic target for LUAD.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: A549 Cells / Adenocarcinoma / Adenocarcinoma of Lung - genetics / Adenocarcinoma of Lung - metabolism / Adenocarcinoma of Lung - pathology / Analysis / Animal experimentation / Animals / Apoptosis / B cells / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cancer therapies / Carcinogenesis / Carcinogenesis - genetics / Care and treatment / Cell cycle / Cell growth / Cell Line, Tumor / Cell migration / Cell Movement / Cell phenotypes / Cell Proliferation / Cholecystokinin / Development and progression / Diagnosis / Flow cytometry / G2 phase / Gene Expression Regulation, Neoplastic / Health aspects / Health Promotion and Disease Prevention / Humans / Infection / Lung adenocarcinoma / Lung cancer / Lung diseases / Lung Neoplasms - genetics / Lung Neoplasms - metabolism / Lung Neoplasms - pathology / Medical prognosis / Medicine/Public Health / Metastases / Metastasis / Mice / Mice, Nude / MicroRNAs / Mortality / Neoplasm Metastasis / Nucleotides / Oncology / Phenotype / Phenotypes / Polymerase chain reaction / RNA / RNA, Transfer - genetics / RNA, Transfer - metabolism / Surgical Oncology / Therapeutic targets / Transfection / Transfer RNA / tRF / tRF-Val-CAC-010 / Tumor growth / Tumor metastasis / Tumorigenesis