C-MYC induces idiopathic pulmonary fibrosis via modulation of miR-9-5p-mediated TBPL1.

We sought to pinpoint the potential role of C-MYC in pulmonary fibroblast proliferation in idiopathic pulmonary fibrosis (IPF) and its mechanism. A mouse model of IPF was established by injection of bleomycin. C-MYC and miR-9-5p expression was determined by RT-qPCR and Western blot analysis. The interaction among C-MYC, miR-9-5p, and TBPL1 was detected by ChIP assay and dual luciferase reporter gene assay. After alteration of C-MYC, miR-9-5p, and TBPL1, their roles in pulmonary fibrosis and collagen fiber deposition in mice as well as proliferation and differentiation of pulmonary fibroblasts were assessed. Upregulated C-MYC expression was seen in the lung tissues of IPF mice and its silencing retarded IPF in mice. C-MYC could activate miR-9-5p that negatively regulated TBPL1 expression. Up-regulated C-MYC promoted proliferation and differentiation of pulmonary fibroblasts by inhibiting TBPL1 via activation of miR-9-5p, thus triggering IPF. Moreover, in the lung tissues-derived cells of IPF mice, C-MYC inhibitor, 10,058-F4, was observed to inhibit miR-9-5p expression, thereby repressing pulmonary fibrosis by up-regulating TBPL1. Our data provided evidence pinpointed the aggravative role of C-MYC in IPF by activating miR-9-5p to regulate TBPL1 expression.