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

Qi,Hongfeng; Wang,Haifeng; Pang,Dabin

doi:10.3892/etm.2019.7738

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

Authors:
- Hongfeng Qi
- Haifeng Wang
- Dabin Pang
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Affiliations: Department of Cardiothoracic Surgery, Changyi People's Hospital, Weifang, Shandong 261300, P.R. China, Department of Endoscopy, Shouguang Hospital of TCM, Shouguang, Shandong 262700, P.R. China
Published online on: July 5, 2019 https://doi.org/10.3892/etm.2019.7738
Pages: 1907-1913

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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.

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