LncRNA FEZF1-AS1 promotes pulmonary fibrosis via up-regulating EZH2 and targeting miR-200c-3p to regulate the ZEB1 pathway.
MicroRNAs
/ genetics
Enhancer of Zeste Homolog 2 Protein
/ metabolism
Humans
RNA, Long Noncoding
/ genetics
Zinc Finger E-box-Binding Homeobox 1
/ genetics
Cell Proliferation
/ genetics
Pulmonary Fibrosis
/ genetics
A549 Cells
Signal Transduction
Transforming Growth Factor beta1
/ metabolism
Cell Movement
/ genetics
Up-Regulation
/ genetics
Epithelial-Mesenchymal Transition
/ genetics
Fibroblasts
/ metabolism
Repressor Proteins
Enhancer of zeste homolog2 (EZH2)
Fibrosis-related proteins
Idiopathic pulmonary fibrosis (IPF)
LncRNA FEZF1-AS1
Zinc finger E-box binding homeobox 1 (ZEB1)
miR-200c-3p
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 10 2024
30 10 2024
Historique:
received:
17
01
2024
accepted:
26
09
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39472569
doi: 10.1038/s41598-024-74570-7
pii: 10.1038/s41598-024-74570-7
doi:
Substances chimiques
MicroRNAs
0
Enhancer of Zeste Homolog 2 Protein
EC 2.1.1.43
MIRN200 microRNA, human
0
RNA, Long Noncoding
0
EZH2 protein, human
EC 2.1.1.43
Zinc Finger E-box-Binding Homeobox 1
0
ZEB1 protein, human
0
Transforming Growth Factor beta1
0
FEZF1 protein, human
0
Repressor Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
26044Subventions
Organisme : National Natural Science Foundation of China
ID : 82205079
Organisme : National Natural Science Foundation of China
ID : 82205079
Organisme : National Natural Science Foundation of China
ID : 82205079
Organisme : National Natural Science Foundation of China
ID : 82205079
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2023QH061
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2023QH061
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2023QH061
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2023QH061
Organisme : Clinical research project of Affiliated Hospital of Weifang Medical College, Shandong Province, China
ID : 2022wyfylcyj05
Organisme : Clinical research project of Affiliated Hospital of Weifang Medical College, Shandong Province, China
ID : 2022wyfylcyj05
Organisme : Clinical research project of Affiliated Hospital of Weifang Medical College, Shandong Province, China
ID : 2022wyfylcyj05
Organisme : Clinical research project of Affiliated Hospital of Weifang Medical College, Shandong Province, China
ID : 2022wyfylcyj05
Organisme : Weifang Municipal Health Commission Traditional Chinese Medicine Research Project
ID : WFZYY2024-4-004
Organisme : Weifang Municipal Health Commission Traditional Chinese Medicine Research Project
ID : WFZYY2024-4-004
Organisme : Weifang Municipal Health Commission Traditional Chinese Medicine Research Project
ID : WFZYY2024-4-004
Organisme : Weifang Municipal Health Commission Traditional Chinese Medicine Research Project
ID : WFZYY2024-4-004
Informations de copyright
© 2024. The Author(s).
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