miR-25 enhances cell migration and invasion in non-small-cell lung cancer cells via ERK signaling pathway by inhibiting KLF4

Ding,Xiaoli; Zhong,Tianyu; Jiang,Lixia; Huang,Junyun; Xia,Yu; Hu,Rong

doi:10.3892/mmr.2018.8772

miR-25 enhances cell migration and invasion in non-small-cell lung cancer cells via ERK signaling pathway by inhibiting KLF4

Authors:
- Xiaoli Ding
- Tianyu Zhong
- Lixia Jiang
- Junyun Huang
- Yu Xia
- Rong Hu
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Affiliations: Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China , Graduate Student Major of Laboratory Medicine of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
Published online on: March 16, 2018 https://doi.org/10.3892/mmr.2018.8772
Pages: 7005-7016
Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In recent years, microRNAs (miRNAs/miRs) have gained increasing interest in cancer research. Increasing evidences demonstrated that miRNAs are important for tumor early detection and prognosis. The present study aimed to explore the function of miR‑25 in non‑small‑cell lung cancer (NSCLC) and its underlying mechanisms. The expression levels of miR‑25 and Krüppel-like factor 4 (KLF4) were assessed in 31 pairs of tissue from patients with NSCLC. In addition, the biological roles of miR‑25 in NSCLC were analyzed via a cell wound healing assay, Transwell invasion and migration assays. Target genes of miR‑25 were predicted using TargetScan and verified via a dual luciferase activity assay, western blotting and reverse transcription‑quantitative polymerase chain reaction. The downstream signaling pathway was confirmed by western blot analysis. In the present study, miR‑25 was overexpressed in 31 NSCLC samples compared with in corresponding normal tissues. Overexpression of miR‑25 using miR‑25 mimics markedly promoted NSCLC cell migration and invasion, while inhibition of miR‑25 exerted the opposite effect. KLF4 was suggested to be a novel target gene of miR‑25 in NSCLC cells. Knockdown of KLF4 promoted the migration and invasion of NSCLC cells, whereas rescue of KLF4 expression reduced cell motion ability in miR‑25‑overexpressing NSCLC cells. Furthermore, it was demonstrated that miR‑25 activated the extracellular signal‑regulated kinase (ERK) signaling pathway, which eventually led to increased vimentin, matrix metalloproteinase 11 and N‑cadherin levels, and the downregulation of E‑cadherin expression by inhibiting the expression of KLF4. In conclusion, miR‑25 was demonstrated to activate the ERK signaling pathway by directly targeting KLF4, promoting cell migration and invasion. The findings of the present study indicated that miR‑25 or KLF4 may serve as a therapeutic target for the treatment of NSCLC.

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