TNF-α inhibits the migration of oral squamous cancer cells mediated by miR-765-EMP3-p66Shc axis.
Whereas TNF-α 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-α at 100ng/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-α increased the expression of miR-765. The upregulation of miR-765 was attributed to the inhibition of the migration. We showed that miR-765 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-α. 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-α 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.
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China.
Zhichao
Z
Zheng
Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Southern Medical University, Guangzhou 510280, China.
Xiuwen
X
Luan
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China.
Jun
J
Zha
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China.
Zhengmao
Z
Li
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China.
Lihong
L
Wu
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China.
Yongyong
Y
Yan
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China.
Haiyan
H
Wang
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China.
Dan
D
Hou
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China.
Liwen
L
Huang
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China.
Feng
F
Huang
National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510640, China; South China Institute of Collaborative Innovation, Dongguan 523808, China.
Huade
H
Zheng
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China.
Linhu
L
Ge
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China. Electronic address: hongbing2015@qq.com.
Hongbing
H
Guan
D020413:3' Untranslated Regions; D000368:Aged; D000070416:Antagomirs / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D020413:3' Untranslated Regions; D000070416:Antagomirs; C485157:EMP3 protein, human; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D034741:RNA, Small Interfering; C528024:SHC1 protein, human; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014409:Tumor Necrosis Factor-alpha
EMP3; MiR-765; Migration; Oral squamous cancer cell; TNF-α; p66Shc