en Radiation Biology Radiation Biology تحقيق بديع Original Research <span style="font-size:10pt"><span style="line-height:119%"><span style="font-family:Calibri"><span style="color:black"><span lang="en-US" style="font-size:12.0pt"><span style="line-height:119%"><span style="font-family:Cambria"><span style="color:#1f497d"><span style="font-weight:bold"><span style="text-transform:uppercase"><span style="language:en-US">ABSTRACT</span></span></span></span></span></span></span></span></span></span></span> <div style="text-align: justify;"><span style="font-size:10pt"><span style="text-justify:newspaper"><span style="text-kashida-space:50%"><span style="line-height:119%"><span style="font-family:Calibri"><span style="color:black"><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Background</span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-weight:bold"><span style="language:en-US">:</span></span></span></span></span> <span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">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. </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Materials and Methods</span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-weight:bold"><span style="language:en-US">:</span></span></span></span></span> <span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">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. </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Results</span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-weight:bold"><span style="language:en-US">:</span></span></span></span></span> <span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">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. </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Conclusion</span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-weight:bold"><span style="language:en-US">:</span></span></span></span></span> <span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">Targeting the miR-34a/CDK6 axis presents a potential therapeutic strategy for RILI.</span></span></span></span></span></span></span></span></span></span></div> GEO dataset, miRNA, protein-protein interaction, RILI. 699 706 http://ijrr.com/browse.php?a_code=A-10-1-1101&slc_lang=en&sid=1 W. Wu 7900319475328460024932 7900319475328460024932 No Department of Nuclear Medicine, The Eighth Medical Center of PLA General Hospital, Beijing, China X. Zhou 7900319475328460024933 7900319475328460024933 No Department of Nuclear Medicine, The Eighth Medical Center of PLA General Hospital, Beijing, China L. Xiao 7900319475328460024934 7900319475328460024934 No Department of Respiratory and Critical Care Medicine，The Eighth Medical Center of PLA General Hospital, Beijing, China P. Bao bao03@163.com 7900319475328460024935 7900319475328460024935 Yes Department of Respiratory and Critical Care Medicine，The Eighth Medical Center of PLA General Hospital, Beijing, China X. Liu liufly301@163.com 7900319475328460024936 7900319475328460024936 No Department of Nuclear Medicine, The Eighth Medical Center of PLA General Hospital, Beijing, China