miR-30c-1* promotes natural killer cell cytotoxicity against human hepatoma cells by targeting the transcription factor HMBOX1

Natural killer (NK) cells play a critical role in antitumor immunity, and the activation of NK cells is regulated by a series of NK cell receptors. Here, we show that crosslinking CD226, an important NK cell receptor, with the anti-CD226 mAb LeoA1 on NKL cells, regulated the expression of several microRNA and transmembrane tumor necrosis factor-α. Among them, miR-30c-1* was noticed because overexpression of miR-30c-1* triggered upregulation of transmembrane tumor necrosis factor-α expression and enhanced NK cell cytotoxicity against hepatoma cell lines SMMC-7721 and HepG2. Furthermore, we proved that the inhibitory transcription factor HMBOX1, which depressed the activation of NK cells, was the direct target gene of miR-30c-1*. In conclusion, our results revealed a novel regulatory mechanism: miR-30c-1* promoted NK cell cytotoxicity against hepatoma cells by targeting HMBOX1. (Cancer Sci 2012; 103: 645–652)