TGF-beta 1 induces CREB1-mediated miR-1290 upregulation to antagonize lung fibrosis via Napsin A

The pathologic mechanisms of pulmonary fibrosis (PF), one of the most common chronic pulmonary diseases, remain unclear. Napsin A is an aspartic proteinase that has been regarded as a hallmark of pulmonary adenocarcinoma. The present study aimed to investigate the specific function and molecular mechanisms of Napsin A in PF from the perspective of microRNA (miRNA or miR) regulation. In the present study, it was found that miR-1290 downregulated the expression of Napsin A by binding to its 3 '-UTR. Cell viability was examined by MTT assay. The protein levels of alpha-smooth muscle actin (alpha-SMA), Collagen I and Napsin A were examined by western blot analysis. The predicted targeting of Napsin A by miR-1290 was validated by luciferase reporter assay. The protein content of alpha-SMA was examined by immunofluorescence staining. miR-1290 was found to be upregulated in blood samples from patients with PF and in TGF-beta 1-stimulated A549 cells. miR-1290 was found to directly target Napsin A. miR-1290 overexpression also significantly promoted A549 cell proliferation and increased the protein levels of markers of fibrosis. Napsin A knockdown exerted effects on A549 cell proliferation and TGF-beta 1-induced fibrosis that were similar to those induced by miR-1290 overexpression; more importantly, Napsin A knockdown significantly reversed the effects of miR-1290 inhibition, indicating that miR-1290 promotes TGF-beta 1-induced fibrosis by targeting Napsin A. Moreover, TGF-beta 1-induced CAMP responsive element binding protein 1 (CREB1) overexpression promoted the transcription of miR-1290 in A549 cells. On the whole, the findings of the present study demonstrate that TGF-beta 1-induced CREB1 over-expression induces the significant upregulation of miR-1290 expression, thus aggravating TGF-beta 1-induced fibrotic changes in A549 cells via the miR-1290 downstream target, Napsin A.