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 transcriptionquantitative (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.

The sirtuin family in health and disease

“…371 In non-small cell LC (NSCLC), the SIRT1-mediated AMPK/mTOR signaling pathway could promote A549 and H1299 cell proliferation, invasion and apoptosis. 372 Expression of SIRT1 can be regulated by ncRNAs, which further influence its effects in regulating cell migration and invasion. For instance, in colorectal cancer (CRC) cells, downregulation of SIRT1, by miR-34a transfection, increases the level of acetylated-p53 and inhibits cell migration and invasion.…”

“… 371 In non-small cell LC (NSCLC), the SIRT1-mediated AMPK/mTOR signaling pathway could promote A549 and H1299 cell proliferation, invasion and apoptosis. 372 …”

Preclinical evidence using synthetic compounds and natural products indicates that AMPK represents a potential pharmacological target for the therapy of pulmonary diseases

“…133 microRNA-217 mimetic inhibited cell proliferation and invasion, promoted apoptosis, and activated AMPK/mTOR in H1299 and A549 cell cultures. 167 Paris saponin VII (PSVII), extracted from Trillium tschonoskii maxim, could inhibit cell viability and colony formation of H460 and PC9 cell cultures, induce apoptosis and autophagy by activating AMPK directly, as also downregulate p-mTOR, p-S6K1, p-4EBP1. 156 Polyphyllin I, extracted from Paris polyphylla, inhibited cell viability and colony formation, induced apoptosis and autophagy through AMPK/mTOR in PC9, H460, and 95D cell cultures, inhibited tumor growth and upregulated the p-AMPK level and LC3 II protein level in the lung tissue of mice.…”

LINC01393, a Novel Long Non-Coding RNA, Promotes the Cell Proliferation, Migration and Invasion through MiR-128-3p/NUSAP1 Axis in Glioblastoma

“…Studies have confirmed that multiple miRNAs can target NUSAP1 acting as an upstream regulators in various malignant tumors except glioma, such as miR-193a-5p [ 6 ], miR-758-3p [ 20 ], miR-569 [ 21 ], and miR-769-5p [ 22 ]. Here, we conducted bioinformatic analysis of TCGA LGG-GBM cohort and ENCORI database and screened that a novel lncRNA LINC01393 which may serve as a sponge for miR-128-3p in the regulation of NUSAP1 expression.…”