Decoding tamoxifen on idiopathic pulmonary fibrosis: integrating network toxicology and multi-omics - PubMed
4 hours ago
- #tamoxifen
- #multi-omics
- #idiopathic pulmonary fibrosis
- Tamoxifen, a breast cancer drug, is investigated for its role in idiopathic pulmonary fibrosis (IPF).
- Integrated methods include computational toxicity prediction, pharmacovigilance, and Mendelian randomization to establish causal links.
- Network toxicology identified seven hubgenes related to miRNA regulation, with EGFR dysregulation as a key finding.
- Multi-omics validation involved transcriptomics, immune infiltration, scRNA sequencing, and machine learning for biomarker identification.
- Mechanistic studies showed miR-432-3p upregulation in IPF, directly targeting EGFR, with tamoxifen binding preferentially to miR-432-3p.
- In vivo studies in mice confirmed tamoxifen-induced pulmonary fibrosis via the miR-432-3p-EGFR axis.
- Tamoxifen promotes IPF through miR-432-3p-mediated EGFR suppression, highlighting environmental and clinical risks.