Exploring the toxicological network of bleomycin-induced pulmonary fibrosis: The role of long non-coding RNAs

Bleomycin (BLM) is an effective anticancer agent; however, its clinical use is limited by its tendency to induce pulmonary fibrosis (PF), a complication whose molecular mechanisms remain unclear. In this study, we established a BLM-induced C57BL/6 mouse model of PF and applied total RNA-seq in combination with network toxicology approaches to investigate the role of long noncoding RNAs (lncRNAs) in this process. The lncRNA Xist was identified as a hub node in the network, regulating the expression of its target Mmp25 via interaction with miR-34a-5p and miR-449c-5p. Further Gene Ontology and KEGG pathway analyses suggested that BLM may promote PF by modulating the TGF-β signaling pathway. Importantly, siRNA-mediated knockdown of Xist in vitro significantly attenuated BLM-induced cellular injury and suppressed TGF-β pathway activation, confirming its functional involvement. These findings provide novel insights into the molecular basis of BLM-induced PF from an lncRNA perspective and highlight Xist as a potential therapeutic target for mitigating the drug's pulmonary toxicity.