miR-30c-1*promotes natural killer cell cytotoxicity against human hepatoma cells by targeting the transcription factor HMBOX1
miR-30c-1*promotes natural killer cell cytotoxicity against human hepatoma cells by targeting the transcription factor HMBOX1
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DOI：
10.1111/j.1349-7006.2012.02207.x
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发表时间：
2012-04-01
期刊：
影响因子：
5.7
通讯作者：
Chen, Lihua
中科院分区：
文献类型：
--
作者：
Gong, Jiuyu;Liu, Rongrong;Chen, Lihua
自然杀伤（NK）细胞在抗肿瘤免疫中起着关键作用，NK细胞的激活受一系列NK细胞受体的调节。在这里，我们表明，交联CD 226，一个重要的NK细胞受体，与抗CD 226 mAb LeoA 1在NKL细胞上，调节几个microRNA和跨膜肿瘤坏死因子-α的表达。其中，miR-30 c-1* 被注意到是因为miR-30 c-1* 的过表达触发跨膜肿瘤坏死因子-a表达的上调，并增强NK细胞对肝癌细胞系SMMC-7721和HepG 2的细胞毒性。进一步证实了抑制NK细胞活化的转录抑制因子HMBOX 1是miR-30 c-1* 的直接靶基因。总之，我们的研究结果揭示了一种新的调控机制：miR-30 c-1* 通过靶向HMBOX 1促进NK细胞对肝癌细胞的细胞毒性。（Cancer Sci 2012; 103：645652）
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-a. Among them, miR-30c-1* was noticed because overexpression of miR-30c-1* triggered upregulation of transmembrane tumor necrosis factor-a 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: 645652)