Comprehensive application of bioinformatics analysis and experimental exploration identifying miR-34a/CDK6 axis as the key regulators for radiation-induced lung injury progression

Background: The pathogenesis of radiation-induced lung injury (RILI) remains elusive. In this study, we aimed to elucidate the mechanism underlying RILI progression by employing a comprehensive approach, integrating bioinformatics analysis and experimental validation. Materials and Methods: Raw transcriptome sequencing data from two Gene Expression Omnibus (GEO) datasets, GSE202586 and GSE14431, were downloaded and overlapping genes were identified. Differential expressions of microRNAs (miRNAs) were analyzed using GEO2R software on the GSE202586 dataset. The miRDB database and miRWalk database were utilized to identify miRNA targets. Specific miRNA inhibitors or protein siRNA were administered to RILI mouse models for experimental confirmation. Results: Ten genes were consistently upregulated in the RILI groups across both datasets. A series of miRNAs were dysregulated in the RILI group, with miR-34a exhibiting the largest difference. By integrating target exploration and protein-protein interaction (PPI) analysis, we determined that the miR-34a/CDK6 axis may be the key regulator of RILI progression. Notably, miR-34a inhibitor treatment significantly alleviated alveolitis in RILI mice, and this effect was substantially reversed by CDK6 siRNA. Conclusion: Targeting the miR-34a/CDK6 axis presents a potential therapeutic strategy for RILI.