ZFPM2, negatively regulated by ZFPM2‐AS1, was downregulated in LUAD and inhibited proliferation, invasion, and EMT. (A) UCSC database showed that ZFPM2 was a nearby gene for ZFPM2‐AS1. (B) The downregulation of ZFPM2 in LUAD samples was obtained in TCGA database. (C, D) RT‐qPCR (mean ± SD; n = 6; Student’s t‐test and one‐way ANOVA) and western blot results of ZFPM2 expression upon ZFPM2‐AS1 overexpression and knockdown in LUAD cells. (E) Downregulation of ZFPM2 expression in LUAD cell lines was detected by RT‐qPCR results (mean ± SD; n = 6; one‐way ANOVA). (F) Knockdown of ZFPM2 by si‐ZFPM2#1/2/3 in A549 cells was confirmed by RT‐qPCR (mean ± SD; n = 6; one‐way ANOVA). (G–I) CCK‐8 (mean ± SD; n = 6; two‐way ANOVA), EdU (scale bar = 100 μm; mean ± SD; n = 6; one‐way ANOVA), and Transwell assays (scale bar = 50 μm; mean ± SD; n = 6; one‐way ANOVA) were used to evaluate the proliferative and invasive abilities of LUAD cells upon ZFPM2 silence. (J, K) IF staining (scale bar = 20 μm; n = 6) and western blot analyses were used to evaluate the expressions of E‐cadherin and N‐cadherin upon ZFPM2 knockdown in LUAD cells. *P < 0.05, **P < 0.01.