Emerging evidence has illustrated that long noncoding RNA (LncRNA) ZEB1 antisense RNA 1 (ZEB1-AS1) involved in the development of various type of human cancers. However, the role of ZEB1-AS1 in non-small cell lung cancer (NSCLC) is still elusive and poorly understood. The present study aimed to provide functional evidence and elucidate the molecular mechanisms by which the ZEB1-AS1 promotes oncogenesis of NSCLC. Our study found that ZEB1-AS1 was upregulated in NSCLC cells and knockdown of ZEB1-AS1 significantly inhibited cell growth and induced cell apoptosis. Mechanically, miR-409-3p was confirmed as a direct target of ZEB1-AS1 and negatively regulated by ZEB1-AS1 via competing endogenous RNA (ceRNA) mechanism; miR-409-3p inhibited ZEB1 expression by directly binding to the 3'UTR. Importantly, as predicted by JASPAR and further confirmed by luciferase reporter gene and ChIP assays, we found ZEB1 could bind to the promoter region of ZEB1-AS1 to activate its expression. Restoration of ZEB1 could partially abolished the action of ZEB1-AS1 silencing on cell proliferation and apoptosis. Collectively, the results suggested that ZEB1-AS1/miR-409-3p/ZEB1 constitutes a positive feedback loop to promote the tumorigenesis of NSCLC, highlighting the possibility of improving NSCLC treatment by targeting the ZEB1-AS1 signaling pathway. (C) 2018 Elsevier Inc. All rights reserved.