Foxp3 downregulation in NSCLC mediates epithelial-mesenchymal transition via NF-κB signaling

Wang,Xi; Liu,Ying; Dai,Lingling; Liu,Qi; Jia,Liuqun; Wang,Huan; An,Lin; Jing,Xiaogang; Liu,Meng; Li,Pengfei; Cheng,Zhe

doi:10.3892/or.2016.5024

Foxp3 downregulation in NSCLC mediates epithelial-mesenchymal transition via NF-κB signaling

Authors:
- Xi Wang
- Ying Liu
- Lingling Dai
- Qi Liu
- Liuqun Jia
- Huan Wang
- Lin An
- Xiaogang Jing
- Meng Liu
- Pengfei Li
- Zhe Cheng
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Affiliations: Department of Respiratory Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
Published online on: August 17, 2016 https://doi.org/10.3892/or.2016.5024
Pages: 2282-2288

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Abstract

Forkhead box P3 (Foxp3) is a member of forkhead box transcription factor family and it was identified as a tumor suppressor in various solid tumors. This study evaluated the expression of Foxp3 in non-small cell lung cancer (NSCLC) and investigated its role in epithelial‑mesenchymal transition (EMT) of cancer cells. qRT-PCR and western blot analysis were used for examining the expression of Foxp3 in NSCLC tissues and the non-tumor tissues. A tissue microarray was constructed and scored for evaluating the clinical significance of Foxp3 expression in NSCLC tissues. RNAi was employed for downregulating Foxp3 expression and cell proliferation was done with MTT assay. Transwell with or without basement membrane matrix was used for cell migration and invasion assay respectively. Foxp3 was found downregulated in NSCLC tissues compared with non-tumoral tissues; downregulation of Foxp3 predicted adverse tumor stage and overall survival; silencing of FOXP3 promoted the proliferation, migration and invasion ability of NSCLC cells and influenced the expression level of EMT-associated proteins. However, forced expression of Foxp3 could reverse this effect. Moreover, Foxp3 could interact with LMO2 and affect the expression level of TAL1, which was in accordance with the findings in T-cell acute lymphoblastic leukemia. By screening the signalling pathways, we observed an obvious upregulation of phosphorylated NF-κB in A549 and H520 cells after silencing of FOXP3. Our results suggest that Foxp3 suppressed NSCLC cell metastasis, at least partially, via NF-κB signaling.

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