LncRNA FEZF1-AS1 promotes pulmonary fibrosis via up-regulating EZH2 and targeting miR-200c-3p to regulate the ZEB1 pathway.

Autor: Liu M; Department of Clinical Laboratory, Affiliated Hospital of Shandong Second Medical University, No. 2428, Yuhe Road, Kuiwen District, Weifang City, 261041, Shandong Province, China., Song L; Department of Rehabilitation Medicine, Affiliated Hospital of Shandong Second Medical University, No. 2428 Yuhe Road, Kuiwen District, Weifang City, 261041, Shandong Province, China., Lai Y; Beijing University of Chinese Medicine, No. 11 on North 3rd Ring Road, Beijing, 100029, China., Gao F; Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Shandong Second Medical University, No. 2428, Yuhe Road, Kuiwen District, Weifang City, 261041, Shandong Province, China. gaofs888@163.com., Man J; Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Shandong Second Medical University, No. 2428, Yuhe Road, Kuiwen District, Weifang City, 261041, Shandong Province, China. manjun0229@126.com.; Clinical Research Center, Affiliated Hospital of Shandong Second Medical University, No. 4948, Shengli East Street, Kuiwen District, Weifang City, 261041, Shandong Province, China. manjun0229@126.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Oct 30; Vol. 14 (1), pp. 26044. Date of Electronic Publication: 2024 Oct 30.
DOI: 10.1038/s41598-024-74570-7
Abstrakt: The role and detailed mechanisms of lncRNAs in idiopathic pulmonary fibrosis (IPF) are not fully understood. qPCR was conducted to verify lncRNA FEZF1-AS1 expression in the transforming growth factor-beta 1 (TGF-β1)-stimulated human lung fibroblasts (HLF) and A549. The EMT-related proteins were performed by western blotting. Cell proliferation, migration, and transition were detected by CCK-8, colony formation, wound-healing and transwell assays. A dual-luciferase reporter assay was conducted to validate the target relationship of FEZF1-AS1 and miR-200c-3p. FEZF1-AS1 is highly expressed in the fibrotic A549 and HLF. in vitro experiments revealed that FEZF1-AS1 facilitates cell proliferation, migration and invasion. Knockdown of FEZF1-AS1 attenuated TGF-b1-induced fibrogenesis both in vitro. Moreover, silencing FEZF1-AS1 inhibited fibrogenesis through modulation of miR-200c-3p. In addition, inhibition of miR-200c-3p promoted fibrogenesis by regulation of Zinc finger E-box binding homeobox 1 (ZEB1). Mechanistically, FEZF1-AS1 promoted lung fibrosis by acting as a competing endogenous RNA (ceRNA) for miR-200c-3p. FEZF1-AS1 silencing increased the expression and activity of miR-200c-3p to inhibit ZEB1 and alleviate lung fibrogenesis in A549 and HLF. In addition, our study showed that FEZF1-AS1 can regulate enhancer of zeste homolog2 (EZH2) to upregulate fibrosis-related proteins and promote lung fibrosis. In summary, the results of our study revealed the pulmonary fibrogenic effect of FEZF1-AS1 in cellular experiments, demonstrating the potential roles and mechanisms of the FEZF1-AS1/miR-200c-3p/ZEB1 and FEZF1-AS1/EZH2 pathways, which provides a novel and potential therapeutic target to lung fibrosis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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