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

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机构: [1]Stomatological 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 [2]The 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 [3]Department of Neurosurgery, Phillips-University Marburg, Baldingerstr, Marburg 35033, Germany [4]Department of Urology, First People’s Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
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关键词: OTSCC hTERT EMT NF-kappa B CRISPR/Cas9

摘要:
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-kappa B 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-kappa B 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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出版当年[2017]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学 3 区 细胞生物学
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Q1 ONCOLOGY Q2 CELL BIOLOGY
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第一作者机构: [1]Stomatological 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 [2]The 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
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