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

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.