Exosomal miR-4687-5p alleviates silica-induced fibrosis by inhibiting EMT via β-catenin targeting

  • Arch Biochem Biophys. 2026 Feb:776:110714. doi: 10.1016/j.abb.2025.110714.
Huiyan Qu  1 ,  Weidong Xie  2 ,  Jing Zhang  3 ,  Zhilin Liu  2 ,  Shuai Chang  2 ,  Fangwei Liu  4
Affiliations
  • 1. Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, China; Yichang Municipal Center for Disease Control & Prevention, Hubei, China.
  • 2. Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, China.
  • 3. Shengjing Hospital, China Medical University, Shenyang, China.
  • 4. Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, China. Electronic address: [email protected].
PMID: 41443291 DOI: 10.1016/j.abb.2025.110714
Abstract

Silicon dioxide (SiO2) is a major occupational hazard causing irreversible pulmonary fibrosis. While epithelial-mesenchymal transition (EMT) is implicated in fibrosis, its regulation remains unclear. This study identified serum exosomal miR-4687-5p as significantly down-regulated in silicosis patients. Dual-luciferase assays confirmed β-catenin as its direct target. Using the exosome inhibitor GW4869, we demonstrated exosome-mediated transfer of miR-4687-5p from macrophages to lung epithelial cells. Treating epithelial cells with a miR-4687-5p mimic revealed its role in modulating EMT by inhibiting β-catenin nuclear translocation. Crucially, silencing β-catenin in murine lung tissue significantly attenuated silica-induced pulmonary fibrosis. Our findings establish that exosomal miR-4687-5p alleviates silicosis-related fibrosis by targeting β-catenin to suppress EMT, highlighting miR-4687-5p as a potential therapeutic target.

Keywords
EMT; Exosome; Silicosis; miRNA.
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