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Zinc finger E-box-binding homeobox 1: its clinical significance and functional role in human thyroid cancer

Authors Zhang Y, Liu G, Wu S, Jiang F, Xie J, Wang Y

Received 20 September 2015

Accepted for publication 24 October 2015

Published 29 March 2016 Volume 2016:9 Pages 1303—1310

DOI https://doi.org/10.2147/OTT.S96723

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Manfred Beleut

Peer reviewer comments 3

Editor who approved publication: Dr William Cho


Yan Zhang,* Gang Liu,* Shihe Wu, Futing Jiang, Jiangping Xie, Yuhong Wang

Department of General Surgery, Navy General Hospital of Chinese PLA, Beijing, People’s Republic of China

*These authors contributed equally to this work

Objective: Transcription factor zinc finger E-box-binding homeobox 1 (ZEB1), as one of the key inducers of epithelial-mesenchymal transition, has been reported to be regulated by microRNA-144 and Bcl-2-associated athanogene 3, which both promote thyroid cancer cell invasion. However, the involvement of ZEB1 in thyroid cancer has not been fully elucidated. In this study, we aimed to investigate the role and clinical implication of ZEB1 in this disease.
Methods: Immunohistochemistry was performed to examine the subcellular localization and the expression level of ZEB1 protein in 82 self-pairs of formalin-fixed and paraffin-embedded cancerous and adjacent noncancerous tissues obtained from patients with thyroid cancer. The roles of ZEB1 in thyroid cancer cell migration, invasion, and proliferation were also detected by transwell and MTT analyses, respectively.
Results: Immunohistochemistry showed that ZEB1 was predominantly localized in the nucleus of thyroid cancer cells. Its immunoreactive score in thyroid cancer tissues was significantly higher than that in adjacent noncancerous tissues (P=0.01). In addition, ZEB1 overexpression was significantly associated with the advanced tumor node metastasis staging (P=0.008), the positive lymph node metastasis (P=0.01) and distant metastasis (P=0.02). Furthermore, ZEB1 knockdown by siRNA could efficiently inhibit the migration, invasion, and proliferation abilities of thyroid cancer cells in vitro.
Conclusion: These findings indicated that ZEB1 might function as an oncogene, the overexpression of which was associated with the aggressive tumor progression of human thyroid cancer. Interestingly, ZEB1 also could promote thyroid cancer cell migration, invasion, and proliferation, suggesting that the inhibition of this protein might be a therapeutic strategy for the treatment of this malignancy.

Keywords: zinc finger E-box-binding homeobox 1, thyroid cancer, migration, invasion, proliferation, immunohistochemistry, small interfering RNA

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