Transcription factor TP63 mediates LncRNA CNTFR-AS1 to promote DNA damage induced by neodymium oxide nanoparticles via homologous recombination repair

The widespread use of neodymium oxide nanoparticles (NPs-Nd₂O₃) has caused environmental pollution and human health problems, thus attracting significant attention. Understanding the mechanisms of NPs- Nd₂O₃-induced genetic damage is of great significance for identifying early markers for NPs- Nd₂O₃-induced lung injury. At present, the mechanisms underlying DNA damage induced by NPs- Nd₂O₃ remain unclear. In this study, we performed functional assays on human bronchial epithelial cells (16HBEs) exposed to various concentrations of NPs-Nd₂O₃ and SD rats administered with a single intratracheal instillation with NPs-Nd₂O₃. Exposure to NPs-Nd₂O₃ 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-Nd₂O₃. Our data verified that transcription factor TP63 mediates the high expression levels of CNTFR-AS1, which in turn regulates NPs-Nd₂O₃-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-Nd₂O₃. Hence, our data provide a basis for the identification of lncRNAs as early diagnostic markers for rare earth lung injury.