miRNA-125b regulates apoptosis of human non-small cell lung cancer via the PI3K/Akt/GSK3β signaling pathway

Wang,Yingyi; Zhao,Ming; Liu,Jieying; Sun,Zhao; Ni,Jianjiao; Liu,Hongsheng

doi:10.3892/or.2017.5808

miRNA-125b regulates apoptosis of human non-small cell lung cancer via the PI3K/Akt/GSK3β signaling pathway

Authors:
- Yingyi Wang
- Ming Zhao
- Jieying Liu
- Zhao Sun
- Jianjiao Ni
- Hongsheng Liu
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Affiliations: Oncology Department of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng, Beijing 100730, P.R. China, Thoracic Surgery Department of China PLA General Hospital, Haidian, Beijing 100853, P.R. China, Peking Union Medical College, Chinese Academy of Medical Sciences, Dongcheng, Beijing 100730, P.R. China, Department of Thoracic Surgery, Peking Union Medical College Hospital, Dongcheng, Beijing 100730, P.R. China
Published online on: July 12, 2017 https://doi.org/10.3892/or.2017.5808
Pages: 1715-1723

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Abstract

The present investigation demonstrated that regulation of microRNA (miR)-125b affected the apoptosis of human non-small cell lung cancer (NSCLC) through targeting of the PI3K/Akt and Wnt/β-catenin signaling pathways. The expression of miR-125b was assessed in patients with NSCLC, which demonstrated that miR-125b expression in NSCLC tissue was higher than that in para-carcinoma tissue. Furthermore, survival analysis of patients with NSCLC over 3 years indicated that the overall survival (OS) and disease-free survival (DFS) rates of patients with low miR-125b expression were higher than those of patients with high miR-125b expression. Proliferation and apoptosis assays were subsequently conducted in the human NSCLC cell line A549 using MTT assay and Annexin V-FITC/PI kits, respectively. Caspase-3 activity ELISA and western blot analysis were also used to assess caspase-3 activity and the protein expression of Bax, Akt, phosphorylated (p)-Akt, p-GSK3β, Wnt and β-catenin. It was observed that downregulation of miR-125b inhibited the proliferation and induced the apoptosis of A549 cells. Downregulation of miR-125b also suppressed the protein expression of p-Akt, Wnt and β-catenin, and increased caspase-3 activity and Bax protein expression in A549 cells. In addition, downregulation of miR-125b combined with the PI3K inhibitor LY294002 enhanced cell growth inhibition, suppression of p-GSK3β, Wnt and β-catenin protein expression and promotion of caspase-3 activity in A549 cells. These results revealed that the downregulation of miR-125b regulates apoptosis in human NSCLC through the suppression of the PI3K/Akt/GSK3β and Wnt/β-catenin signaling pathways.

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