TGF‑β1 induces CREB1‑mediated miR‑1290 upregulation to antagonize lung fibrosis via Napsin A

Guan,Shuhong; Wu,Yudi; Zhang,Qiudi; Zhou,Jun

doi:10.3892/ijmm.2020.4565

TGF‑β1 induces CREB1‑mediated miR‑1290 upregulation to antagonize lung fibrosis via Napsin A

Authors:
- Shuhong Guan
- Yudi Wu
- Qiudi Zhang
- Jun Zhou
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Affiliations: Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Changzhou, Jiangsu 213000, P.R. China
Published online on: April 3, 2020 https://doi.org/10.3892/ijmm.2020.4565
Pages: 141-148
Copyright: © Guan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 α‑smooth muscle actin (α‑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 α‑SMA was examined by immunofluorescence staining. miR‑1290 was found to be upregulated in blood samples from patients with PF and in TGF‑β1‑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‑β1‑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‑β1‑induced fibrosis by targeting Napsin A. Moreover, TGF‑β1‑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‑β1‑induced CREB1 overexpression induces the significant upregulation of miR‑1290 expression, thus aggravating TGF‑β1‑induced fibrotic changes in A549 cells via the miR‑1290 downstream target, Napsin A.

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