MiR-125b-5p alleviates pulmonary fibrosis by inhibiting TGFβ1-mediated epithelial-mesenchymal transition via targeting BAK1.

Abstract

This study explores the role and potential mechanisms of microRNA-125b-5p (miR-125b-5p) in pulmonary fibrosis (PF). PF is a typical outcome of many chronic lung diseases, with poor prognosis and the lack of appropriate medical treatment because PF's molecular mechanisms remain poorly understood. In this study, using in vitro and in vivo analyses, we find that miR-125b-5p is likely a potent regulator of lung fibrosis. The findings reveal that, on the one hand, miR-125b-5p not only specifically decreases in the epithelial-mesenchymal transition (EMT) of lung epithelial cells, but also shows a downregulation trend in the lung tissues of mice with PF. On the other hand, overexpression of miR-125b-5p on the cellular and animal levels downregulates EMT and fibrotic phenotypes, respectively. To clarify the molecular mechanism of the "therapeutic" effect of miR-125b-5p, we use the target prediction tool combined with a dual luciferase assay and complete a rescue experiment by constructing the overexpression vector of the target gene Bcl-2 homologous antagonist/ killer (BAK1), thus confirming that miR-125b-5p can effectively inhibit EMT and fibrosis process by targeting BAK1 gene. MiR-125b-5p inhibits the EMT in lung epithelial cells by negatively regulating BAK1, while overexpression of miR-125b-5p can alleviate lung fibrosis. The findings suggest that MiR-125b-5p/BAK1 can serve as a potential treatment target for PF.