Background
Idiopathic pulmonary fibrosis (IPF) is an unrepairable disease that
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.
Methods
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.
Results
DNM3OS was upregulated by transforming growth factor beta 1 (TGF-β1) in a dose- and time-dependent manner. DNM3OS knockdown repressed the growth and migration of lung fibroblast, and fibrotic gene expression (CoL1α1, CoL3α1, α-SMA, vimentin, and fibronectin), while suppression of TSC2 accelerated the above process. DNM3OS 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.