Title |
microRNA-889 is downregulated by histone deacetylase inhibitors and confers resistance to natural killer cytotoxicity in hepatocellular carcinoma cells
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Published in |
Methods in Cell Science, May 2017
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DOI | 10.1007/s10616-017-0108-1 |
Pubmed ID | |
Authors |
Haitao Xie, Qiugui Zhang, Hui Zhou, Jun Zhou, Ji Zhang, Yan Jiang, Jinghong Wang, Xianglin Meng, Leping Zeng, Xiaoxin Jiang |
Abstract |
Major histocompatibility complex class I chain-related gene B (MICB) is expressed on tumor cells and participates in natural killer (NK) cell-mediated antitumor immune response through engagement with the NKG2D receptor. This study was undertaken to identify novel microRNA (miRNA) regulators of MICB and clarify their functions in NK cell-mediated cytotoxicity to hepatocellular carcinoma (HCC) cells. Bioinformatic analysis and luciferase reporter assay were conducted to search for MICB-targeting miRNAs. Overexpression and knockdown experiments were performed to determine the roles of candidate miRNAs in the susceptibility of HCC cells to NK lysis. miR-889 was identified as a novel MICB-targeting miRNA and overexpression of miR-889 significantly inhibited the mRNA and protein expression of MICB in HepG2 and SMMC7721 HCC cells. miR-889 expression had a negative correlation with MICB mRNA levels in HCC specimens (r = -0.392, P = 0.0146). NK cell-mediated cytotoxicity was reduced in miR-889-overexpressing HCC cells, which was reversed by restoration of MICB expression. In contrast, knockdown of miR-889 led to more pronounced NK cell-mediated lysis in HCC cells. HCC cells exposed to the histone deacetylase (HDAC) inhibitor sodium valproate showed downregulation of miR-889. Enforced expression of miR-889 prevented the upregulation of MICB and enhancement of NK cell-mediated lysis by HDAC inhibitors. In conclusion, miR-889 upregulation attenuates the susceptibility of HCC cells to NK lysis and represents a potential target for improving NK cell-based antitumor therapies. |
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Members of the public | 3 | 100% |
Mendeley readers
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Germany | 1 | 8% |
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Demographic breakdown
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Student > Ph. D. Student | 3 | 23% |
Researcher | 2 | 15% |
Student > Master | 2 | 15% |
Student > Bachelor | 1 | 8% |
Other | 1 | 8% |
Other | 0 | 0% |
Unknown | 4 | 31% |
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Immunology and Microbiology | 2 | 15% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 8% |
Agricultural and Biological Sciences | 1 | 8% |
Medicine and Dentistry | 1 | 8% |
Other | 0 | 0% |
Unknown | 5 | 38% |