Transcription factor TP63 mediates LncRNA CNTFR-AS1 to promote DNA damage induced by neodymium oxide nanoparticles via homologous recombination repair
Lei Gao, Xia Zhang, Jinjin Cui, Ling Liu, Dapeng Tai, Suhua Wang, Lihua Huang
Abstract
The widespread use of neodymium oxide nanoparticles (NPs-Nd 2 O 3 ) has caused environmental pollution and human health problems, thus attracting significant attention. Understanding the mechanisms of NPs- Nd 2 O 3 -induced genetic damage is of great significance for identifying early markers for NPs- Nd 2 O 3 -induced lung injury. At present, the mechanisms underlying DNA damage induced by NPs- Nd 2 O 3 remain unclear. In this study, we performed functional assays on human bronchial epithelial cells (16HBEs) exposed to various concentrations of NPs-Nd 2 O 3 and SD rats administered with a single intratracheal instillation with NPs-Nd 2 O 3 . Exposure to NPs-Nd 2 O 3 could lead to DNA damage in 16HBE cells and rat lung tissue cells. We found a novel long non-coding RNA, named CNTFR-AS1, which was highly expressed after exposure to NPs-Nd 2 O 3 . Our data verified that transcription factor TP63 mediates the high expression levels of CNTFR-AS1, which in turn regulates NPs-Nd 2 O 3 -induced DNA damage in cells by inhibiting HR repair. Moreover, the levels of CNTFR-AS1 were correlated with the number of years worked by occupational workers. Collectively, these results demonstrate that CNTFR-AS1 acts as a novel DNA damage regulator in bronchial epithelial cells exposed to NPs-Nd 2 O 3 . Hence, our data provide a basis for the identification of lncRNAs as early diagnostic markers for rare earth lung injury.