Open AccessmiR‐30c‐1* promotes natural killer cell cytotoxicity against human hepatoma cells by targeting the transcription factor HMBOX 1
Author(s) -
Gong Jiuyu,
Liu Rongrong,
Zhuang Ran,
Zhang Yun,
Fang Liang,
Xu Zhuwei,
Jin Liang,
Wang Tao,
Song Chaojun,
Yang Kun,
Wei Yuying,
Yang Angang,
Jin Boquan,
Chen Lihua
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02207.x
Subject(s) - cytotoxicity , natural killer cell , microbiology and biotechnology , tumor necrosis factor alpha , transcription factor , cell , chemistry , cancer research , downregulation and upregulation , receptor , lymphokine activated killer cell , interleukin 21 , cytotoxic t cell , cell culture , biology , immunology , gene , in vitro , biochemistry , genetics
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)