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

Abstract 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 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-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.