Differential Effects of Histone Deacetylases on the Expression of NKG2D Ligands and NK Cell-Mediated Anticancer Immunity in Lung Cancer Cells

被引:20
作者
Cho, Haeryung [1 ,2 ]
Son, Woo-Chang [3 ]
Lee, Young-Shin [1 ]
Youn, Eun Jung [1 ,2 ]
Kang, Chi-Dug [1 ]
Park, You-Soo [3 ]
Bae, Jaeho [1 ,2 ]
机构
[1] Pusan Natl Univ, Dept Biochem, Sch Med, Yangsan 50612, South Korea
[2] Pusan Natl Univ, PNU GRAND Convergence Med Sci Educ Res Ctr, Sch Med, Yangsan 50612, South Korea
[3] Dongnam Inst Radiol & Med Sci, Dept Res Ctr, Busan 46033, South Korea
基金
新加坡国家研究基金会;
关键词
HDAC; lung cancer; NK cell; NKG2D ligands; CHROMOBACTERIUM-VIOLACEUM NO-968; INHIBITOR; DEPSIPEPTIDE; APOPTOSIS; FR901228; HDACS;
D O I
10.3390/molecules26133952
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Histone acetylation is an epigenetic mechanism that regulates the expression of various genes, such as natural killer group 2, member D (NKG2D) ligands. These NKG2D ligands are the key molecules that activate immune cells expressing the NKG2D receptor. It has been observed that cancer cells overexpress histone deacetylases (HDACs) and show reduced acetylation of nuclear histones. Furthermore, HDAC inhibitors are known to upregulate the expression of NKG2D ligands. Humans have 18 known HDAC enzymes that are divided into four classes. At present, it is not clear which types of HDAC are involved in the expression of NKG2D ligands. We hypothesized that specific types of HDAC genes might be responsible for altering the expression of NKG2D ligands. In this study, we monitored the expression of NKG2D ligands and major histocompatibility complex (MHC) class I molecules in lung cancer cells which were treated with six selective HDAC inhibitors and specific small interfering RNAs (siRNAs). We observed that treatment with FK228, which is a selective HDAC1/2 inhibitor, also known as Romidepsin, induced NKG2D ligand expression at the transcriptional and proteomic levels in two different lung cancer cell lines. It also caused an increase in the susceptibility of NCI-H23 cells to NK cells. Silencing HDAC1 or HDAC2 using specific siRNAs increased NKG2D ligand expression. In conclusion, it appears that HDAC1 and HDAC2 might be the key molecules regulating the expression of NKG2D ligands. These results imply that specifically inhibiting HDAC1 and HDAC2 could induce the expression of NKG2D ligands and improve the NK cell-mediated anti-cancer immunity.
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页数:13
相关论文
共 30 条
[1]   A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas [J].
Balasubramanian, S. ;
Ramos, J. ;
Luo, W. ;
Sirisawad, M. ;
Verner, E. ;
Buggy, J. J. .
LEUKEMIA, 2008, 22 (05) :1026-1034
[2]   Histone Deacetylase Inhibitor Modulates NKG2D Receptor Expression and Memory Phenotype of Human Gamma/Delta T Cells Upon Interaction With Tumor Cells [J].
Bhat, Jaydeep ;
Dubin, Samuel ;
Dananberg, Alexandra ;
Quabius, Eiger Susanne ;
Fritsch, Juergen ;
Dowds, C. Marie ;
Saxena, Ankit ;
Chitadze, Guranda ;
Lettau, Marcus ;
Kabelitz, Dieter .
FRONTIERS IN IMMUNOLOGY, 2019, 10
[3]   Targeting histone deacetylase 8 as a therapeutic approach to cancer and neurodegenerative diseases [J].
Chakrabarti, Alokta ;
Melesina, Jelena ;
Kolbinger, Fiona R. ;
Oehme, Ina ;
Senger, Johanna ;
Witt, Olaf ;
Sippl, Wolfgang ;
Jung, Manfred .
FUTURE MEDICINAL CHEMISTRY, 2016, 8 (13) :1609-1634
[4]  
Chen Hong Ping, 2015, Critical Reviews in Oncogenesis, V20, P35
[5]   Lung Cancer: Epidemiology, Etiology, and Prevention [J].
Dela Cruz, Charles S. ;
Tanoue, Lynn T. ;
Matthay, Richard A. .
CLINICS IN CHEST MEDICINE, 2011, 32 (04) :605-+
[6]  
Furumai R, 2002, CANCER RES, V62, P4916
[7]   Roles of the immune system in cancer: from tumor initiation to metastatic progression [J].
Gonzalez, Hugo ;
Hagerling, Catharina ;
Werb, Zena .
GENES & DEVELOPMENT, 2018, 32 (19-20) :1267-1284
[8]   NKG2D ligands:: key targets of the immune response [J].
Gonzalez, Segundo ;
Lopez-Soto, Alejandro ;
Suarez-Alvarez, Beatriz ;
Lopez-Vazquez, Antonio ;
Lopez-Larrea, Carlos .
TRENDS IN IMMUNOLOGY, 2008, 29 (08) :397-403
[9]   Prior alcohol use enhances vulnerability to compulsive cocaine self-administration by promoting degradation of HDAC4 and HDAC5 [J].
Griffin, Edmund A., Jr. ;
Melas, Philippe A. ;
Zhou, Royce ;
Li, Yang ;
Mercado, Peter ;
Kempadoo, Kimberly A. ;
Stephenson, Stacy ;
Colnaghi, Luca ;
Taylor, Kathleen ;
Hu, Mei-Chen ;
Kandel, Eric R. ;
Kandel, Denise B. .
SCIENCE ADVANCES, 2017, 3 (11)
[10]   Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation [J].
Haggarty, SJ ;
Koeller, KM ;
Wong, JC ;
Grozinger, CM ;
Schreiber, SL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (08) :4389-4394