Long non-coding RNA (lncRNAs), which are increasingly identified to be dysregulated in cancers, has been verified to participate in tumorigenesis and cancer development. LncRNA TTN-AS1 has been validated as an oncogene in several cancers, such as esophageal squamous cell carcinoma and cervical cancer. Here, we studied the role of TTN-AS1 in lung adenocarcinoma (LAD). The online website UCSC, NCBI and NONCODE displayed that TTN-AS1 is poorly expressed in normal lung tissue. Furtherly, we found a remarkable increase of TTN-AS1 expression in LAD cell lines in comparison with BEAS-2B cells. Functionally, silencing TTN-AS1 resulted in inhibited cell proliferation and migration in LAD cells. Mechanically, TTN-AS1 knockdown enhanced the level of PTEN protein while reduced p-AKT level. Meanwhile, PTEN inhibition observably recovered the repressive effect of TTN-AS1 silence on the biological behaviors of A549 cells. What's more, we demonstrated that TTN-AS1 modulated PTEN expression not at mRNA level but protein level. Intriguingly, TTN-AS1 was uncovered to reduce PTEN stability via inhibiting the interactivity of PTEN with MAGI2. Jointly, our findings unveiled that TTN-AS1 plays a carcinogenic part in LAD progression through destabilizing PTEN protein so as to activate PI3K/AKT pathway, therefore indicating TTN-AS1 as a promising target for LAD treatment. (C) 2019 Elsevier Inc. All rights reserved.