The Role of miR-497/EIF3A Axis in TGFβ1-Induced Epithelial-Mesenchymal Transition and Extracellular Matrix in Rat Alveolar Epithelial Cells and Pulmonary Fibroblasts.

Multi-cause-induced interstitial lung disease, particularly pulmonary fibrosis, is a serious clinical concern. Fibroblasts have been suggested to have a major role, with it recently being revealed that some of these fibroblasts are derived from alveolar epithelial cells through epithelial-mesenchymal transition (EMT). Eukaryotic translation initiation factor 3 subunit A (EIF3A) is a protein that in humans is encoded by the EIF3A gene, and has been suggested to play roles in regulating translation of a subset of mRNAs and in regulating cell cycle progression and cell proliferation. In the present study, we chose a well-known TGFβ1-induced EMT model in alveolar epithelial cells to investigate the functional role of EIF3A. TGFβ1-induced EIF3A expression and EMT process in alveolar epithelial cells, after EIF3A knockdown, the EMT process could be partially reversed. Online tools and luciferase assays showed that miR-497 could inhibit EIF3A expression by directly binding to the 3'UTR of EIF3A. Ectopic miR-497 expression partially reversed TGFβ1-induced EMT in alveolar epithelial cells. In addition, miR-497 could suppress TGFβ1-induced pulmonary fibroblast proliferation and EIF3A, Collagen I and α-SMA protein levels. Taken together, EIF3A could promote TGFβ1-induced EMT in alveolar epithelial cells; miR-497 suppressed TGFβ1-induced EMT in alveolar epithelial cells TGFβ1-induced excessive proliferation and ECM in pulmonary fibroblast through inhibiting EIF3A by targeting. MiR-497/EIF3A axis shows the potential to be effective in the treatment of pulmonary fibrosis. J. Cell. Biochem. 118: 3401-3408, 2017.