HOXA5 -induced lncRNA DNM3OS promotes human embryo lung fibroblast fibrosis via recruiting EZH2 to epigenetically suppress TSC2 expression

• Published in: Journal of thoracic disease 2024-02, Vol.16 (2), p.1234-1246
• Main Authors: Lv, Hong, Qian, Xingjia, Tao, Zhengzheng, Shu, Jun, Shi, Dongfang, Yu, Jing, Fan, Guiqin, Qian, Qiuhong, Shen, Luhong, Lu, Bing
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 2072-1439; 2077-6624
• DOI: 10.21037/jtd-23-1145

Idiopathic pulmonary fibrosis (IPF) is an unrepairable disease that results in lung dysfunction and decreased quality of life. Prevention of pulmonary fibrosis is challenging, while its pathogenesis remains largely unknown. Herein, we investigated the effect and mechanism of long non-coding RNA (lncRNA) /Antisense RNA in the pathogenesis of pulmonary fibrosis. EdU (5-ethynyl-2'-deoxyuridine) and wound healing assays were employed to evaluate the role of DNM3OS on cell proliferation and migration. Western blot detected the proteins expressions of alpha-smooth muscle actin (α-SMA), vimentin, and fibronectin. The interactions among genes were evaluated by RNA pull-down, luciferase reporter, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and chromatin Isolation by RNA purification (ChIRP) assays. was upregulated by transforming growth factor beta 1 (TGF-β1) in a dose- and time-dependent manner. knockdown repressed the growth and migration of lung fibroblast, and fibrotic gene expression ( , , α-SMA, vimentin, and fibronectin), while suppression of accelerated the above process. DNM3OS recruited EZH2 to the promoter region of , increased the occupancy of EZH2 and H3K27me3, and thereby suppressed the expression of . promoted the transcription of . -induced promoted the proliferation, migration, and expression of fibrosis-related genes in human embryo lung fibroblast via recruiting EZH2 to epigenetically suppress the expression of .