TNF-alpha inhibits the migration of oral squamous cancer cells mediated by miR-765-EMP3-p66Shc axis

Zheng Zhichao; Luan Xiuwen; Zha Jun; Li Zhengmao; Wu Lihong; Yan Yongyong; Wang Haiyan; Hou Dan; Huang Liwen; Huang Feng; Zheng Huade; Ge Linhu; Guan Hongbing

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TNF-alpha inhibits the migration of oral squamous cancer cells mediated by miR-765-EMP3-p66Shc axis

机译：TNF-α抑制MiR-765-EMP3-P66SHC轴介导的口腔鳞状癌细胞的迁移

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Whereas TNF-alpha can facilitate the metastasis of oral squamous cancer cells (OSCC), whether it inhibits the metastasis is not clear so far. In this study, we demonstrated that high dose TNF-alpha at 100 ng/mL could in vitro significantly inhibit the migration of two OSCC cell lines, CAL-27 and SCC-25. To explore the related mechanisms, we focused on the involvement of the microRNAs and found that TNF-a increased the expression of miR-765. The upregulation of miR-765 was attributed to the inhibition of the migration. We showed that miR765 directly targeted EMP3 and suppressed its expression. We also found that the expression of EMP3 was much higher in human oral squamous cancer in compare with the surrounding normal tissue. Interestingly, p66Shc, a downstream molecule in the EMP3-related signaling pathway, was increased by TNF-alpha. We found that the overexpression of p66Shc could suppress the migration through the enhanced E-cadherin and ZO-1 signals. Either silencing the expression of EMP3 or enhancing the expression of miR-765 could upregulate the expression of p66Shc. Together, our results demonstrated that TNF-alpha inhibited the metastasis of oral squamous cancer cell through the miR-765-EMP3-p66Shc axis, which may provide new insights for the therapy of oral squamous cancer.

机译：尽管TNF-α可以促进口腔鳞癌细胞（OSCC）的转移，但其是否抑制转移目前尚不清楚。在这项研究中，我们证明100 ng/mL的高剂量TNF-α在体外可显著抑制两种OSCC细胞系CAL-27和SCC-25的迁移。为了探索相关机制，我们重点研究了microRNA的参与，发现TNF-a增加了miR-765的表达。miR-765的上调归因于对迁移的抑制。我们发现miR765直接靶向EMP3并抑制其表达。我们还发现，与周围正常组织相比，EMP3在人类口腔鳞癌中的表达要高得多。有趣的是，TNF-α增加了EMP3相关信号通路的下游分子p66Shc。我们发现p66Shc的过度表达可以通过增强的E-cadherin和ZO-1信号抑制迁移。无论是沉默EMP3的表达还是增强miR-765的表达都可以上调p66Shc的表达。总之，我们的结果表明TNF-α通过miR-765-EMP3-p66Shc轴抑制口腔鳞癌细胞的转移，这可能为口腔鳞癌的治疗提供新的见解。

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来源
《Cellular Signalling》 |2017年第1期|共8页
作者
Zheng Zhichao; Luan Xiuwen; Zha Jun; Li Zhengmao; Wu Lihong; Yan Yongyong; Wang Haiyan; Hou Dan; Huang Liwen; Huang Feng; Zheng Huade; Ge Linhu; Guan Hongbing;
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作者单位

Guangzhou Med Univ Guangzhou Inst Oral Dis Key Lab Oral Med Stomatol Hosp Guangzhou 510140 Guangdong Peoples R China;

Southern Med Univ Dept Oral &

Maxillofacial Surg Affiliated Stomatol Hosp Guangzhou 510280 Guangdong Peoples R China;

Guangzhou Med Univ Guangzhou Inst Oral Dis Key Lab Oral Med Stomatol Hosp Guangzhou 510140 Guangdong Peoples R China;

Guangzhou Med Univ Guangzhou Inst Oral Dis Key Lab Oral Med Stomatol Hosp Guangzhou 510140 Guangdong Peoples R China;

Guangzhou Med Univ Guangzhou Inst Oral Dis Key Lab Oral Med Stomatol Hosp Guangzhou 510140 Guangdong Peoples R China;

Guangzhou Med Univ Guangzhou Inst Oral Dis Key Lab Oral Med Stomatol Hosp Guangzhou 510140 Guangdong Peoples R China;

Guangzhou Med Univ Guangzhou Inst Oral Dis Key Lab Oral Med Stomatol Hosp Guangzhou 510140 Guangdong Peoples R China;

Guangzhou Med Univ Guangzhou Inst Oral Dis Key Lab Oral Med Stomatol Hosp Guangzhou 510140 Guangdong Peoples R China;

Guangzhou Med Univ Guangzhou Inst Oral Dis Key Lab Oral Med Stomatol Hosp Guangzhou 510140 Guangdong Peoples R China;

Guangzhou Med Univ Guangzhou Inst Oral Dis Key Lab Oral Med Stomatol Hosp Guangzhou 510140 Guangdong Peoples R China;

South China Univ Technol Natl Engn Res Ctr Tissue Restorat &

Reconstruct Guangzhou 510640 Guangdong Peoples R China;

Guangzhou Med Univ Guangzhou Inst Oral Dis Key Lab Oral Med Stomatol Hosp Guangzhou 510140 Guangdong Peoples R China;

Guangzhou Med Univ Guangzhou Inst Oral Dis Key Lab Oral Med Stomatol Hosp Guangzhou 510140 Guangdong Peoples R China;

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原文格式 PDF
正文语种 eng
中图分类细胞形态学;
关键词
TNF-alpha; MiR-765; EMP3; p66Shc; Migration; Oral squamous cancer cell;

机译：TNF-alpha;mir-765;emp3;p66shc;迁移;口腔鳞状癌细胞;

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机译：CXC趋化因子-7抑制口腔舌鳞状细胞癌细胞的生长和迁移，由上皮 - 间充质转换信号通路介导
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机译：RhoA和RalB参与香叶基香叶基转移酶I抑制剂介导的人类口腔鳞状细胞癌细胞增殖和迁移的抑制
7. The Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor ZD1839 (Iressa) Suppresses Proliferation and Invasion of Human Oral Squamous Carcinoma Cells via p53 Independent and MMP, uPAR Dependent Mechanism [C] . EUN JU LEE, JIN HA WHANG, NAM KYEONG JEON, Meeting on Cell Signaling World: Signal Transduction Pathways as Therapeutic Targets . 2007

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9. Knockdown of Long Non-Coding RNA (lncRNA) Colon Cancer-Associated Transcript-1 (CCAT1) Suppresses Oral Squamous Cell Carcinoma Proliferation Invasion and Migration by Inhibiting the Discoidin Domain Receptor 2 (DDR2)/ERK/AKT Axis [O] . Mingyu Sun, Zhenyu Shen 2020

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10. Knockdown of Long Non-Coding RNA (lncRNA) Colon Cancer-Associated Transcript-1 (CCAT1) Suppresses Oral Squamous Cell Carcinoma Proliferation, Invasion, and Migration by Inhibiting the Discoidin Domain Receptor 2 (DDR2)/ERK/AKT Axis [O] . Mingyu Sun, Zhenyu Shen 2020

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11. Combined Therapy for Non-Resectable Squamous Cell Carcinoma of the Oral Cavity. Local Selective Intra-Arterial Infusion with Adriamycin and Bleomycin Combined Concurrently with Radiotherapy. The Predictive Value of Flow Cytometry in Monitoring Cell Cycle Kinetic Effects of Therapy [R] . Noorman van der Dussen, M. F. 1986

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TNF-alpha inhibits the migration of oral squamous cancer cells mediated by miR-765-EMP3-p66Shc axis

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