MicroRNA-217 inhibits the proliferation and invasion, and promotes apoptosis of non-small cell lung cancer cells by targeting sirtuin 1.

Abstract

Non-small cell lung cancer (NSCLC) is a common malignancy worldwide. MicroRNA (miR)-217 and sirtuin 1 (SIRT1) have been reported to play significant roles in different types of cancer, such as osteosarcoma and prostate cancer; however, the association between miR-217 and SIRT1 in the cell proliferation, apoptosis and invasion of NSCLC remain unknown. Thus, the present study aimed to investigate the roles of miR-217 and SIRT1 in NSCLC. The expression levels of miR-217 and SIRT1 were detected via reverse transcription-quantitative (RT-q)PCR and western blot analyses. The effect of miR-217 on A549 and H1299 cell proliferation, apoptosis and invasion was assessed via the Cell Counting Kit-8, flow cytometry and Transwell assays, respectively. In addition, the association between SIRT1 and miR-217 was predicted using the TargetScan database, and verified via the dual-luciferase reporter assay, and RT-qPCR and western blot analyses. The results demonstrated that miR-217 expression was significantly downregulated, while SIRT1 expression was significantly upregulated in A549 and H1299 cells compared with the human bronchial epithelial cells. Furthermore, transfection with miR-217 mimic significantly inhibited A549 and H1299 cell proliferation and invasion, and induced A549 and H1299 cell apoptosis. The results of the dual-luciferase reporter assay and western blot analysis confirmed that SIRT1 is a target gene of miR-217. In addition, miR-217 inhibited the activation of AMP-activated protein kinase (AMPK) and mTOR signaling. Taken together, the results of the present study suggest that miR-217 inhibits A549 and H1299 cell proliferation and invasion, and induces A549 and H1299 cell apoptosis by targeting SIRT1 and inactivating the SIRT1-mediated AMPK/mTOR signaling pathway. Thus, miR-217 may be used as a potential therapeutic target for the treatment of patients with NSCLC.