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.
Department of Immunology, Fourth Military Medical University, Xi'an, China.
Jiuyu
J
Gong
Rongrong
R
Liu
Ran
R
Zhuang
Yun
Y
Zhang
Liang
L
Fang
Zhuwei
Z
Xu
Liang
L
Jin
Tao
T
Wang
Chaojun
C
Song
Kun
K
Yang
Yuying
Y
Wei
Angang
A
Yang
Boquan
B
Jin
Lihua
L
Chen
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology*; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism; D000098862:T Lineage-Specific Activation Antigen 1
D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; C512050:HMBOX1 protein, human; D018398:Homeodomain Proteins; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha