microRNA-889 is downregulated by histone deacetylase inhibitors and confers resistance to natural killer cytotoxicity in hepatocellular carcinoma cells

microRNA-889 is downregulated by histone deacetylase inhibitors and confers resistance to natural... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cytotechnology Springer Journals

microRNA-889 is downregulated by histone deacetylase inhibitors and confers resistance to natural killer cytotoxicity in hepatocellular carcinoma cells

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Publisher
Springer Journals
Copyright
Copyright © 2017 by Springer Science+Business Media Dordrecht
Subject
Chemistry; Biotechnology; Biomedicine, general; Biochemistry, general
ISSN
0920-9069
eISSN
1573-0778
D.O.I.
10.1007/s10616-017-0108-1
Publisher site
See Article on Publisher Site

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.

Journal

CytotechnologySpringer Journals

Published: May 26, 2017

References

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