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ABSTRACT
Long non-coding RNAs (lncRNA) exert biological functions by interacting with RNAs, proteins, and DNA. Although lung damage associated with radon exposure was attributed to disturbances in microRNA and protein expression, the influence of radon on lncRNA is at present not known. The aim of this study was to (1) examine the effect of radon on lncRNA-mediated expression of transcription factors in mRNA in mouse lung tissue and (2) determine potential function and targets. Female BALB/c mice were divided into two groups: control and radon exposure to approximately 100,000 Bq/m3 (equivalent up to 60 working level month, WLM).RNA was extracted from lung tissue and used for high through-put lncRNA microarray analysis. A total of 1256 lncRNA transcripts were differentially expressed between the two groups of mice. Among these, the top 200 lncRNA–mRNA sets, with fold change of >2 and p-value <.05, were selected for KEGG analysis. Functional analysis via bioinformatics prediction in this study also suggested involvement of ErbB and Notch pathways in radon-induced mouse pulmonary injury. The results from immunohistochemical and Western blot analysis indicated that EbB2 and k-Ras protein expressions were significantly increased. In conclusion, approximately 1,000 dysregulated lncRNA transcripts were found in radon-exposed mice and these lncRNA may play an important role in lung damage following radon exposure. The observations in this study also suggested that ErbB2 and Notch pathways are activated and may be involved in radon-induced pulmonary toxicity.
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Acknowledgments
The lncRNAs microarray hybridization and bioinformatics analysis were conducted by OE Biotech Co Ltd (Shanghai, China). This research was supported by National Science Foundation of China (81573178, 81673203 and 81673126).