Background: 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) DNM3OS /Antisense RNA in the pathogenesis of pulmonary fibrosis. Methods: EdU (5-ethynyl-2'-deoxyuridine) and wound healing assays were employed to evaluate the role of DNM30S on cell proliferation and migration. Western blot detected the proteins expressions of alphasmooth muscle actin (alpha-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. Results: DNM3OS was upregulated by transforming growth factor beta 1 (TGF-beta 1) in a dose- and timedependent manner. DNM3OS knockdown repressed the growth and migration of lung fibroblast, and fibrotic gene expression ( CoL1 alpha 1 , CoL3 alpha 1 , alpha-SMA, vimentin, and fibronectin), while suppression of TSC2 accelerated the above process. DNM30S recruited EZH2 to the promoter region of TSC2 , increased the occupancy of EZH2 and H3K27me3, and thereby suppressed the expression of TSC2 . HOXA5 promoted the transcription of DNM3OS . Conclusions: HOXA5 -induced DNM3OS promoted the proliferation, migration, and expression of fibrosis -related genes in human embryo lung fibroblast via recruiting EZH2 to epigenetically suppress the expression of TSC2 .
