MicroRNAs (miR) are known to be critical regulators in tumor progression. miR-7-5p was reported to be involved in several cancers, including glioblastoma, cervical cancer, and melanoma, but its prognostic value and biological function in non-small-cell lung cancer (NSCLC) remain unclear. In this study, using quantitative real-time PCR analysis, we found that miR-7-5p was significantly downregulated in NSCLC tissues and cell lines. Lower miR-7-5p expression was associated with tumor-node-metastasis stage and tumor size by chi-squared test. Deceased miR-7-5p expression was associated with a worse prognosis in patients with NSCLC using Kaplan-Meier survival analysis and multivariate Cox regression analysis. Experiments in NSCLC cell lines (A549 and H1299) demonstrated that upregulation of miR-7-5p significantly suppressed cell proliferation, but induced cell cycle G0/G1 phase arrest and apoptosis using Cell Counting Kit-8, colony formation, and flow cytometry analysis. Through loss-of-function assays, we further demonstrated that downregulation of miR-7-5p promoted cell proliferation and cell cycle G1/S transition, but decreased cell apoptosis in SPC-A1 cells. Furthermore, P21-activated kinase 2 (PAK2) was predicted and confirmed as a direct target gene of miR-7-5p in NSCLC cells by luciferase reporter assay. In addition, we found PAK2 overexpression could partially reverse the effects of miR-7-5p on cell proliferation, cell cycle distribution, and apoptosis. We thus concluded that lower expression of miR-7-5p was associated with poor prognosis and NSCLC progression by directly targeting PAK2.
Keywords: PAK2; cell proliferation; miR-7-5p; non-small-cell lung cancer.
© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.