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MTBP promotes migration and invasion by regulation of ZEB2-mediated epithelial–mesenchymal transition in lung cancer cells

Authors Pan B, Han H, Wu L, Xiong Y, Zhang J, Dong B, Yang Y, Chen J

Received 12 March 2018

Accepted for publication 9 July 2018

Published 10 October 2018 Volume 2018:11 Pages 6741—6756

DOI https://doi.org/10.2147/OTT.S167963

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 4

Editor who approved publication: Dr Jianmin Xu


Bo Pan,1,2 Haibo Han,1,3 Lina Wu,1,4 Ying Xiong,1,2 Jianzhi Zhang,1,2 Bin Dong,1,4 Yue Yang,1,2 Jinfeng Chen1,2

1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China; 2Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China; 3Department of Biobank, Peking University Cancer Hospital & Institute, Beijing, China; 4Department of Central Laboratory, Peking University Cancer Hospital & Institute, Beijing, China

Background: It is clearly necessary to discover prognostic biomarkers to identify stage I patients at risk of recurrence and give them timely postoperative treatment.
Materials and methods: Data of stage I lung adenocarcinoma were retrieved from four gene series in Gene Expression Omnibus (GEO) database (GSE50081, GSE30219, GSE37745, and GSE13213). Partek Genomics Suite software was used to identify survival-related genes for finding candidate indicators for early-stage patients at risk of recurrence. Differential expression of MTBP (MDM2 binding protein) in early-stage lung adenocarcinoma tissues was determined by immunohistochemical staining. The effects of MTBP interference expression and overexpression on viability, migration, and invasion capacity of lung cells were evaluated using Cell Counting Kit-8, wound healing, and Transwell assays. The tumor growth and lung metastasis in vivo were observed in chick embryo chorioallantoic membrane model. Human Exon 2.0 ST Array was used to analyze downstream regulation genes of MTBP in lung cancer cells. Involvement of ZEB2 and epithelial–mesenchymal transition (EMT) markers was investigated by Western blot.
Results: By mining GEO database, we identified MTBP as a poor prognostic indicator of stage I lung adenocarcinomas. In addition, increased expression of MTBP was also associated with poor survival in our early-stage lung adenocarcinoma cohort. Further experiment suggested that knockdown of MTBP suppressed the migration and invasion of A549 and H1975 cells in vitro and in vivo, whereas overexpression of MTBP in HCC827 and PC9 cells promoted the migration and invasion in vitro and in vivo. Furthermore, ZEB2 upregulation directly activated EMT to mediate the downstream effects of MTBP involved in lung cancer cells metastasis.
Conclusion: MTBP is an independent indicator for poor prognosis in stage I lung adenocar­cinomas and might promote the aggressive phenotype of non-small-cell lung cancer by inducing the EMT process through upregulating ZEB2 expression.

Keywords: stage I lung cancer, MTBP, metastasis, ZEB2

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