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Objective To investigate the effects of long non-coding RNA FEZ family zinc finger 1 antisense RNA 1(lncRNA FEZF1-AS1) on enhancer of zeste homolog 2(EZH2) in regulation of proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of pulmonary interstitial cells and its mechanism. Methods The A549 cells human lung adenocarcinoma cell line were divided into control group and model group [model cells were induced into lung interstitial cells after being treated with transforming growth factor β1(TGF-β1)20 ng/mL for 48 h]. The protein expression of E-cadherin, N-cadherin and vimentin in each group was detected by Western blot. The expression of lncRNA FEZF1-AS1 and EZH2 in the two groups was detected by RT-qPCR. Cells in the transfection group were divided into si NC group,lncRNA FEZF1-AS1+OE vector group and si lncRNA FEZF1-AS1+OE EZH2 group. Cell proliferation was examined by CCK-8 method, cell migration was detected by cell scratch, and cell invasion was detected by Transwell assays. The protein expression of E-cadherin, N-cadherin, vimentin and EZH2 in each group was detected by Western blot. The direct binding effect of FEZF1-AS1 and EZH2 was determined by RNA immuno-precipitation (RIP). Results Compared with the control group, the protein expression level of E-cadherin in the model group was significantly decreased (P＜0.05),and the protein expression of N-cadherin and vimentin was significantly increased(P＜0.05). Compared with the control group, the expression level of lncRNA FEZF1-AS1 and EZH2 genes was significantly increased in the model group (P＜0.05). Compared with si NC group, the proliferation, migration and invasion ability of si lncRNA FEZF1-AS1+OE vector group were decreased, the expression of E-cadherin protein was increased while the expression of N-cadherin, vimentin and EZH2 was decreased(P＜0.05). Compared with si lncRNA FEZF1-AS1+OE vector group, the proliferation, invasion and migration of si lncRNA FEZF1-AS1+OE EZH2 group were increased (P＜0.05). E-cadherin expression was decreased, while N-cadherin, vimentin and EZH2 expressions were increased (P＜0.05). RIP experiment further confirmed that lncRNA FEZF1-AS1 had direct binding effect with EZH2. Conclusions LncRNA FEZF1-AS1 can promote the proliferation, invasion, metastasis and EMT process of pulmonary fibrosis cells by regulating EZH2.