Oncotarget

Research Papers:

Telomerase reverse transcriptase mediates EMT through NF-κB signaling in tongue squamous cell carcinoma

Yan Wu, Chunxiang Bian, Chunlin Zhen, Liu Liu, Zhenghong Lin, Muhammad Farrukh Nisar, Mei Wang, Jörg W. Bartsch, Enyi Huang, Ping Ji, Li Yang, Yanhong Yu, Junfeng Yang, Xuemei Jiang and Julia Li Zhong _

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Oncotarget. 2017; 8:85492-85503. https://doi.org/10.18632/oncotarget.20888

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Abstract

Yan Wu1,2,*, Chunxiang Bian1,2,*, Chunlin Zhen1,2, Liu Liu2, Zhenghong Lin2, Muhammad Farrukh Nisar2, Mei Wang2, Jörg W. Bartsch3, Enyi Huang1, Ping Ji1, Li Yang2, Yanhong Yu4, Junfeng Yang4, Xuemei Jiang2 and Julia Li Zhong2

1Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of High Education, Chongqing, 401147, China

2The Base of “111 Project” for Biomechanics and Tissue Repair Engineering, Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering college, Life Science College, Chongqing University, Chongqing 400044, China

3Department of Neurosurgery, Phillips-University Marburg, Baldingerstr, Marburg 35033, Germany

4Department of Urology, First People’s Hospital of Yunnan Province, Kunming, Yunnan, 650032, China

*These authors contributed equally to this work and should both be considered as first authors

Correspondence to:

Julia Li Zhong, email: jlzhong@cqu.edu.cn

Xuemei Jiang, email: jiangxuemei@cqu.edu.cn

Keywords: OTSCC, hTERT, EMT, NF-κB, CRISPR/Cas9

Received: May 09, 2017     Accepted: August 26, 2017     Published: September 14, 2017

ABSTRACT

Locoregional lymph nodes metastasis in oral tongue squamous cell carcinoma represents one of important and common prognostic factors for poor clinical outcome. The human Telomerase Reverse Transcriptase (hTERT) is one of key players in cancer metastasis and stemness, but its exact function in tongue squamous cell carcinoma remains unknown. Here, we aim to understand the role of hTERT by utilizing the CRISPR/Cas9 gene editing system to deplete hTERT in the SCC-15 cell line. Functional comparison of SCC-15 control and knockout cells (hTERT−/−) showed that loss of hTERT suppressed cell proliferation and migration/invasion. Furthermore, hTERT depletion significantly decreased tumorigenesis, including alterations in cellular morphology that areindicative for epithelial-mesenchymal transition (EMT). Mechanistically we demonstrated that the hTERT knockout attenuates NF-κB signaling via a negative feedback regulation in tumorprogression. From these results we propose a novel molecular mechanism of hTERT to promote SCC-15 invasion and metastasis via NF-κB activation. We conclude that targeting hTERT may represent a new therapeutic strategy to improve therapy and survival of tongue squamous cell carcinoma patients.


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