LncRNA-PVT1 activates lung fibroblasts via miR-497-5p and is facilitated by FOXM1.
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| Abstract |
It is little known about the lncRNA-PVT1 effect on occupational pulmonary fibrosis, although researches show it plays an essential role in cancer. Studies reveal that lung fibroblast activation is one of the key events in silica-induced fibrosis. Here, we found that lncRNA-PVT1 promoted the proliferation, activation, and migration of lung fibroblasts. The isolation of cytoplasmic and nuclear RNA assay and fluorescence in situ hybridization experiment showed that lncRNA-PVT1 was abundantly expressed in the cytoplasm. Luciferase reporter gene assay and RNA pull-down experiment indicated that the cytoplasmic-localized lncRNA-PVT1 could competitively bind miR-497-5p. MiR-497-5p was further observed to attenuate silica-induced pulmonary fibrosis by targeting Smad3 and Bcl2. Moreover, the transcription factor FOXM1 acted as a profibrotic factor by elevating lncRNA-PVT1 transcription in lung fibroblasts. Inhibition of FOXM1 expression with thiostrepton alleviated silica-induced pulmonary fibrosis in vivo. Collectively, we revealed that FOXM1-facilitated lncRNA-PVT1 activates lung fibroblasts via miR-497-5p during silica-induced pulmonary fibrosis, which may provide potential therapeutic targets for pulmonary fibrosis.
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| Authors | Yan Li, Wenqing Sun, Honghong Pan, Jiali Yuan, Qi Xu, Tiantian Xu, Ping Li, Demin Cheng, Yi Liu, Chunhui Ni |
| Journal | Ecotoxicology and environmental safety (Ecotoxicol Environ Saf) Vol. 213 Pg. 112030 (Apr 15 2021) ISSN: 1090-2414 [Electronic] Netherlands |
| PMID | 33601175 (Publication Type: Journal Article) |
| Copyright | Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. |
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