We herein identified PTEN as a direct target of miR-21-5p, and miR-21-5p inhibitor upregulated PTEN and inactivated PI3K/AKT signaling and reversed MEG3-knockdown induced PTEN downregulation and PI3K/AKT signaling activation in NSCLC cells. This evidence concerns the gene AKT1 and non-small cell lung carcinoma.