miR‑448 promotes progression of non‑small‑cell lung cancer via targeting SIRT1

Abstract

Deregulation of microRNAs (miRs) has been demonstrated to be involved in both the initiation and the development of non-small-cell lung cancer (NSCLC). miR-448 has been identified as a tumor suppressor in several cancer types. The aim of the present study was to explore the role of miR-448 in NSCLC. Tumor tissues and paired normal tissues were obtained from patients with NSCLC. The viability and migration of A549 cells were determined by the Cell Counting kit-8 and wound-healing assays, respectively. Gene and protein levels were detected by reverse transcription-quantitative polymerase chain reaction analysis and western blotting, respectively. The interaction between the 3′ untranslated region of sirtuin1 (SIRT1) and miR-448 was predicted by TargetScan and verified by dual luciferase reporter assay. miR-448 levels were revealed to be decreased whereas SIRT1 levels were increased in NSCLC tissues compared with normal tissues. Pearson's correlation analysis demonstrated that there was a negative correlation between miR-448 and SIRT1 mRNA levels. Overexpression of miR-448 led to reduced growth and migration ability of A549 cells. In addition, overexpression of miR-448 decreased SIRT1 mRNA and protein levels, thereby inhibiting epithelial-mesenchymal transition (EMT) and affecting EMT-associated molecules, including vimentin and E-cadherin. Dual luciferase reporter assay confirmed that SIRT1 was a direct target of miR-448. Notably, activation of SIRT1 by resveratrol treatment partially reversed the cell growth inhibition induced by miR-448 mimics. These findings suggested that the progression of NSCLC may be controlled by miR-448, which appears to hold promise as a therapeutic target for patients with NSCLC.