Potential Functions of the tRNA-Derived Fragment tRF-Gly-GCC Associated With Oxidative Stress in Radiation-Induced Lung Injury

Dose Response. 2022 Sep 23;20(3):15593258221128744. doi: 10.1177/15593258221128744. eCollection 2022 Jul-Sep.

Abstract

Objective: Transfer RNA-derived small RNAs (tsRNAs) are a novel type of non-coding RNA with various regulatory functions. They are associated with oxidative stress in various diseases, but their potential functions in radiation-induced lung injury (RILI) remain uncertain.

Methods: To explore the role of tsRNAs in RILI, we used X-rays to irradiate human bronchial epithelial cells and examined the expression profile of altered tsRNAs by RNA sequencing and bioinformatics analysis. Sequencing results were verified by qRT-PCR. tsRNA functions were explored using several methods, including CCK-8, reactive oxygen species (ROS) assays, cell transfection, and western blotting.

Results: Eighty-six differentially expressed tRNA-derived fragments (tRFs) were identified: 64 were upregulated, and 22 were downregulated. Among them, the regulation of tRF-Gly-GCC, associated with oxidative stress, may be mediated by the inhibition of cell proliferation, promotion of ROS production, and apoptosis in the occurrence and development of RILI. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that the underlying molecular mechanism may involve the PI3K/AKT and the FOXO1 signaling pathways.

Conclusion: Our findings provide new insights into the molecular mechanisms underpinning RILI, advancing the clinical prevention and treatment of this disease.

Keywords: oxidative stress; radiation-induced lung injury; tRF-Gly-GCC; tRNA-derived fragment; tRNA-derived small RNAs.