Research Paper Volume 12, Issue 14 pp 14808—14818
Hsa_circ_0044226 knockdown attenuates progression of pulmonary fibrosis by inhibiting CDC27
- 1 Department of Geriatrics, Peking University First Hospital, Beijing 100034, China
Received: February 12, 2020 Accepted: June 1, 2020 Published: July 24, 2020https://doi.org/10.18632/aging.103543
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Copyright © 2020 Qi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disorder. Here, we performed a bioinformatics analysis using the GSE102660 dataset from the Gene Expression Omnibus database to identify differentially expressed circRNAs (DEcircRNAs) in tissues from IPF patients and healthy controls. The results identified 45 DEcircRNAs, among which expression of hsa_circ_0044226 was markedly higher in lung tissues from IPF patients than from healthy controls. Knocking down hsa_circ_0044226 expression using a targeted shRNA inhibited TGF-β1-induced fibrosis in RLE-6TN cells and in a bleomycin-induced mouse model of IPA. The diminished TGF-β1-induced fibrosis was associated with upregulated expression of E-cadherin and downregulated expression of α-SMA, collagen III and fibronectin 1, as well as with reduced expression of CDC27, suggesting inhibition of epithelial-to-mesenchymal transition (EMT). All of those effects were reversed by overexpression of CDC27. This suggests CDC27 overexpression abolishes the antifibrotic effect of hsa_circ_0044226 knockdown through activation of EMT. Furthermore, hsa_circ_0044226 knockdown decreased the expression of CDC27 in BLM-induced pulmonary fibrosis mouse model. Collectively then, these findings indicate that downregulation of hsa_circ_0044226 attenuates pulmonary fibrosis in vitro and in vivo by inhibiting CDC27, which in turn suppresses EMT. This suggests hsa_circ_0044226 may be a useful therapeutic target for the treatment of IPF.