Abstract
BackgroundRadon is a known human lung carcinogen, whose underlying carcinogenic mechanism remains unclear. Recently, circular RNA (circRNA), a class of endogenous non-protein coding RNAs that contain a circular loop, was found to exhibit multiple biological effects. In this study, circRNA profiles in mouse lung tissues between control and radon exposure were analyzed.MethodsSix mice were exposed to radon at concentration of 100,000 Bq/m3, 12 h/d, for up to cumulative doses of 60 working level months (WLM). H&E staining and immunohistochemistry of caspase-3 were used to detect the damages in lung tissue. The lung tissue of control and exposed group were selected for circRNA microarray study. The circRNA/microRNA interaction was analyzed by starBase prediction software. 5 highest expressing circRNAs were selected by real-time PCR to validate the consistency in mouse lung tissue exposed to radon.ResultsInflammatory reaction was found in mouse lung tissue exposed to radon, and caspase-3 expression was significantly increased. Microarray screening revealed 107 up-regulated and 83 down-regulated circRNAs, among which top 30 circRNAs with the highest fold changes were chosen for further analysis, with 5 microRNAs binding sites listed for each circRNA. Consistency of the top 5 circRNAs with the highest expressions were confirmed in mice exposed with 60WLM of radon.ConclusionMouse lung tissue was severely injured when exposed to radon through pathological diagnosis and immunohistochemical analysis. A series of differentially expressed circRNAs demonstrated that they may play an important role in pulmonary toxicity induced by radon.
Highlights
Radon is a known human lung carcinogen, whose underlying carcinogenic mechanism remains unclear
We aimed to determine the damages in mouse lung tissue and the changes in circular RNA (circRNA) expression profiles upon exposure to radon, in order to explore their potential functions in radon-induced lung damage
Alteration in histological pathology of mouse lung tissue The hematoxylin and eosin (H&E) stainings of lung tissues from mice exposed to 60 working level months (WLM) radon displayed inflammatory cells in the alveolus interval (Fig. 1A. b: black arrow) and some alveolar septal fracture (Fig. 1A. b: red arrow)
Summary
Radon is a known human lung carcinogen, whose underlying carcinogenic mechanism remains unclear. CircRNA profiles in mouse lung tissues between control and radon exposure were analyzed. The lung tissue of control and exposed group were selected for circRNA microarray study. 5 highest expressing circRNAs were selected by real-time PCR to validate the consistency in mouse lung tissue exposed to radon. Radon is the most notorious environmental radioactive gas and has been categorized by the World Health Organization as a carcinogenic substance that causes lung cancer. Α particles could affect lung tissue and may cause lung cancer via DNA and oxidative damages [5, 6]. The causative effect of radon on lung cancer and its specific mechanisms remain unclear, and one of the carcinogenic mechanisms.
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