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BioMed Research International
Volume 2016, Article ID 8797206, 15 pages
http://dx.doi.org/10.1155/2016/8797206
Review Article

HDAC Inhibitors as Epigenetic Regulators of the Immune System: Impacts on Cancer Therapy and Inflammatory Diseases

1Biomedical Sciences Program, Midwestern University, 19555 N 59th Avenue, Glendale, AZ 85308, USA
2Department of Microbiology & Immunology, Arizona College of Osteopathic Medicine, Midwestern University, 19555 N 59th Avenue, Glendale, AZ 85308, USA

Received 20 February 2016; Revised 8 June 2016; Accepted 29 June 2016

Academic Editor: Masahiko Hatano

Copyright © 2016 Elizabeth E. Hull et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Fournel, C. Bonfils, Y. Hou et al., “MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo,” Molecular Cancer Therapeutics, vol. 7, no. 4, pp. 759–768, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. D. M. Vigushin, S. Ali, P. E. Pace et al., “Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo,” Clinical Cancer Research, vol. 7, no. 4, pp. 971–976, 2001. View at Google Scholar · View at Scopus
  3. N. Sato, T. Ohta, H. Kitagawa et al., “FR901228, a novel histone deacetylase inhibitor, induces cell cycle arrest and subsequent apoptosis in refractory human pancreatic cancer cells,” International Journal of Oncology, vol. 24, no. 3, pp. 679–685, 2004. View at Google Scholar · View at Scopus
  4. H. J. Kwon, T. Owa, C. A. Hassig, J. Shimada, and S. L. Schreiber, “Depudecin induces morphological reversion of transformed fibroblasts via the inhibition of histone deacetylase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 7, pp. 3356–3361, 1998. View at Publisher · View at Google Scholar · View at Scopus
  5. Z. R. Schoepflin, I. M. Shapiro, and M. V. Risbud, “Class I and IIa HDACs mediate HIF-1α stability through PHD2-dependent mechanism, while HDAC6, a class IIb member, promotes HIF-1α transcriptional activity in nucleus pulposus cells of the intervertebral disc,” Journal of Bone and Mineral Research, vol. 31, no. 6, pp. 1287–1299, 2016. View at Publisher · View at Google Scholar
  6. C. F. Deroanne, K. Bonjean, S. Servotte et al., “Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling,” Oncogene, vol. 21, no. 3, pp. 427–436, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. A. Wassef, D. J. Watson, P. Morrison, S. Bryant, and J. Flack, “Neuroleptic-valproic acid combination in treatment of psychotic symptoms: a three-case report,” Journal of Clinical Psychopharmacology, vol. 9, no. 1, pp. 45–48, 1989. View at Google Scholar · View at Scopus
  8. M. Schroeder, M. O. Krebs, S. Bleich, and H. Frieling, “Epigenetics and depression: current challenges and new therapeutic options,” Current Opinion in Psychiatry, vol. 23, no. 6, pp. 588–592, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Darvishi, T. Tiraihi, S. A. Mesbah-Namin, A. Delshad, and T. Taheri, “Decreased GFAP expression and improved functional recovery in contused spinal cord of rats following valproic acid therapy,” Neurochemical Research, vol. 39, no. 12, pp. 2319–2333, 2014. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Y. Lee, S. Maeng, S. R. Kang et al., “Valproic acid protects motor neuron death by inhibiting oxidative stress and endoplasmic reticulum stress-mediated cytochrome c release after spinal cord injury,” Journal of Neurotrauma, vol. 31, no. 6, pp. 582–594, 2014. View at Publisher · View at Google Scholar · View at Scopus
  11. N. Khan, M. Jeffers, S. Kumar et al., “Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors,” Biochemical Journal, vol. 409, no. 2, pp. 581–589, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. P. Drogaris, V. Villeneuve, C. Pomiès et al., “Histone deacetylase inhibitors globally enhance H3/H4 tail acetylation without affecting H3 lysine 56 acetylation,” Scientific Reports, vol. 2, article 220, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. B. Barneda-Zahonero and M. Parra, “Histone deacetylases and cancer,” Molecular Oncology, vol. 6, no. 6, pp. 579–589, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. H. Liu, Q. Hu, A. J. D'Ercole, and P. Ye, “Histone deacetylase 11 regulates oligodendrocyte-specific gene expression and cell development in OL-1 oligodendroglia cells,” GLIA, vol. 57, no. 1, pp. 1–12, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. A. Villagra, F. Cheng, H.-W. Wang et al., “The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance,” Nature Immunology, vol. 10, no. 1, pp. 92–100, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. L. Bosch-Presegué and A. Vaquero, “The dual role of sirtuins in cancer,” Genes and Cancer, vol. 2, no. 6, pp. 648–662, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. L. R. Saunders and E. Verdin, “Sirtuins: critical regulators at the crossroads between cancer and aging,” Oncogene, vol. 26, no. 37, pp. 5489–5504, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. M. S. Longworth and L. A. Laimins, “Histone deacetylase 3 localizes to the plasma membrane and is a substrate of Src,” Oncogene, vol. 25, no. 32, pp. 4495–4500, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. X. Zhang, Z. Yuan, Y. Zhang et al., “HDAC6 modulates cell motility by altering the acetylation level of cortactin,” Molecular Cell, vol. 27, no. 2, pp. 197–213, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. F. X. Soriano, S. Chawla, P. Skehel, and G. E. Hardingham, “SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites,” Journal of Neurochemistry, vol. 124, no. 1, pp. 26–35, 2013. View at Publisher · View at Google Scholar · View at Scopus
  21. C. Choudhary, C. Kumar, F. Gnad et al., “Lysine acetylation targets protein complexes and co-regulates major cellular functions,” Science, vol. 325, no. 5942, pp. 834–840, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. I. V. Gregoretti, Y.-M. Lee, and H. V. Goodson, “Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis,” Journal of Molecular Biology, vol. 338, no. 1, pp. 17–31, 2004. View at Publisher · View at Google Scholar · View at Scopus
  23. M. A. Glozak, N. Sengupta, X. Zhang, and E. Seto, “Acetylation and deacetylation of non-histone proteins,” Gene, vol. 363, pp. 15–23, 2005. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Ocker, “Deacetylase inhibitors-focus on non-histone targets and effects,” World Journal of Biological Chemistry, vol. 1, no. 5, pp. 55–61, 2010. View at Publisher · View at Google Scholar
  25. K. Ververis, A. Hiong, T. C. Karagiannis, and P. V. Licciardi, “Histone deacetylase inhibitors (HDACIS): multitargeted anticancer agents,” Biologics, vol. 7, no. 1, pp. 47–60, 2013. View at Publisher · View at Google Scholar · View at Scopus
  26. K. Nakane, Y. Fujita, R. Terazawa et al., “Inhibition of cortactin and SIRT1 expression attenuates migration and invasion of prostate cancer DU145 cells,” International Journal of Urology, vol. 19, no. 1, pp. 71–79, 2012. View at Publisher · View at Google Scholar · View at Scopus
  27. B. P. Ashburner, S. D. Westerheide, and A. S. Baldwin Jr., “The p65 (RelA) subunit of NF-κB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression,” Molecular and Cellular Biology, vol. 21, no. 20, pp. 7065–7077, 2001. View at Publisher · View at Google Scholar · View at Scopus
  28. J. von Burstin, S. Eser, M. C. Paul et al., “E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex,” Gastroenterology, vol. 137, no. 1, pp. 361–371.e5, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. K. J. Falkenberg and R. W. Johnstone, “Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders,” Nature Reviews Drug Discovery, vol. 13, no. 9, pp. 673–691, 2014. View at Publisher · View at Google Scholar · View at Scopus
  30. A. C. West and R. W. Johnstone, “New and emerging HDAC inhibitors for cancer treatment,” The Journal of Clinical Investigation, vol. 124, no. 1, pp. 30–39, 2014. View at Publisher · View at Google Scholar · View at Scopus
  31. N. Ahuja, A. R. Sharma, and S. B. Baylin, “Epigenetic therapeutics: a new weapon in the war against cancer,” Annual Review of Medicine, vol. 67, no. 1, pp. 73–89, 2016. View at Publisher · View at Google Scholar · View at Scopus
  32. S. Yoon and G. H. Eom, “HDAC and HDAC inhibitor: from cancer to cardiovascular diseases,” Chonnam Medical Journal, vol. 52, no. 1, pp. 1–11, 2016. View at Publisher · View at Google Scholar
  33. E. Hu, E. Dul, C.-M. Sung et al., “Identification of novel isoform-selective inhibitors within class I histone deacetylases,” Journal of Pharmacology and Experimental Therapeutics, vol. 307, no. 2, pp. 720–728, 2003. View at Publisher · View at Google Scholar · View at Scopus
  34. D. Wegener, C. Hildmann, and A. Schwienhorst, “Recent progress in the development of assays suited for histone deacetylase inhibitor screening,” Molecular Genetics and Metabolism, vol. 80, no. 1-2, pp. 138–147, 2003. View at Publisher · View at Google Scholar · View at Scopus
  35. K. Hoffmann, G. Brosch, P. Loidl, and M. Jung, “A non-isotopic assay for histone deacetylase activity,” Nucleic Acids Research, vol. 27, no. 9, pp. 2057–2058, 1999. View at Publisher · View at Google Scholar · View at Scopus
  36. B. D. Marks, S. A. Fakhoury, W. J. Frazee, H. C. Eliason, and S. M. Riddle, “A substrate-independent TR-FRET histone deacetylase inhibitor assay,” Journal of Biomolecular Screening, vol. 16, no. 10, pp. 1247–1253, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. D. Riester, C. Hildmann, A. Schwienhorst, and F.-J. Meyer-Almes, “Histone deacetylase inhibitor assay based on fluorescence resonance energy transfer,” Analytical Biochemistry, vol. 362, no. 1, pp. 136–141, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. R. Furumai, A. Matsuyama, N. Kobashi et al., “FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases,” Cancer Research, vol. 62, no. 17, pp. 4916–4921, 2002. View at Google Scholar · View at Scopus
  39. M. Yoshida, M. Kijima, M. Akita, and T. Beppu, “Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A,” The Journal of Biological Chemistry, vol. 265, no. 28, pp. 17174–17179, 1990. View at Google Scholar · View at Scopus
  40. T. Beckers, C. Burkhardt, H. Wieland et al., “Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group,” International Journal of Cancer, vol. 121, no. 5, pp. 1138–1148, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Ni, E. Esposito, V. P. Raj et al., “New macrocyclic analogs of the natural histone deacetylase inhibitor FK228; design, synthesis and preliminary biological evaluation,” Bioorganic & Medicinal Chemistry, vol. 23, no. 21, pp. 6785–6793, 2015. View at Publisher · View at Google Scholar · View at Scopus
  42. K. Saijo, T. Katoh, H. Shimodaira, A. Oda, O. Takahashi, and C. Ishioka, “Romidepsin (FK228) and its analogs directly inhibit phosphatidylinositol 3-kinase activity and potently induce apoptosis as histone deacetylase/phosphatidylinositol 3-kinase dual inhibitors,” Cancer Science, vol. 103, no. 11, pp. 1994–2001, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. B. C. Valdez, J. E. Brammer, Y. Li et al., “Romidepsin targets multiple survival signaling pathways in malignant T cells,” Blood Cancer Journal, vol. 5, article e357, 2015. View at Publisher · View at Google Scholar
  44. C. M. Adams, S. W. Hiebert, and C. M. Eischen, “Myc induces miRNA-mediated apoptosis in response to HDAC inhibition in hematologic malignancies,” Cancer Research, vol. 76, no. 3, pp. 736–748, 2016. View at Publisher · View at Google Scholar · View at Scopus
  45. K. Nishida, T. Komiyama, S.-I. Miyazawa et al., “Histone deacetylase inhibitor suppression of autoantibody-mediated arthritis in mice via regulation of p16INK4a and p21 WAF1/Cip1 expression,” Arthritis and Rheumatism, vol. 50, no. 10, pp. 3365–3376, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. Y.-L. Chung, M.-Y. Lee, A.-J. Wang, and L.-F. Yao, “A therapeutic strategy uses histone deacetylase inhibitors to modulate the expression of genes involved in the pathogenesis of rheumatoid arthritis,” Molecular Therapy, vol. 8, no. 5, pp. 707–717, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. T. Ciossek, H. Julius, H. Wieland, T. Maier, and T. Beckers, “A homogeneous cellular histone deacetylase assay suitable for compound profiling and robotic screening,” Analytical Biochemistry, vol. 372, no. 1, pp. 72–81, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Bantscheff, C. Hopf, M. M. Savitski et al., “Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes,” Nature Biotechnology, vol. 29, no. 3, pp. 255–265, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. F. Leoni, A. Zaliani, G. Bertolini et al., “The antitumor histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits antiinflammatory properties via suppression of cytokines,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 5, pp. 2995–3000, 2002. View at Publisher · View at Google Scholar · View at Scopus
  50. F. Leoni, G. Fossati, E. C. Lewis et al., “The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo,” Molecular Medicine, vol. 11, no. 1-12, pp. 1–15, 2005. View at Publisher · View at Google Scholar · View at Scopus
  51. T. Sanda, T. Okamoto, Y. Uchida et al., “Proteome analyses of the growth inhibitory effects of NCH-51, a novel histone deacetylase inhibitor, on lymphoid malignant cells,” Leukemia, vol. 21, no. 11, pp. 2344–2353, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. J.-H. Cho, M. Dimri, and G. P. Dimri, “MicroRNA-31 is a transcriptional target of histone deacetylase inhibitors and a regulator of cellular senescence,” Journal of Biological Chemistry, vol. 290, no. 16, pp. 10555–10567, 2015. View at Publisher · View at Google Scholar · View at Scopus
  53. X.-N. Li, Q. Shu, J. M.-F. Su, L. Perlaky, S. M. Blaney, and C. C. Lau, “Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expression of p21Cip1, CDK4, and CMYC,” Molecular Cancer Therapeutics, vol. 4, no. 12, pp. 1912–1922, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. Y. Zhai, X. Chen, D. Yu et al., “Histone deacetylase inhibitor valproic acid promotes the induction of pluripotency in mouse fibroblasts by suppressing reprogramming-induced senescence stress,” Experimental Cell Research, vol. 337, no. 1, pp. 61–67, 2015. View at Publisher · View at Google Scholar · View at Scopus
  55. M. Malvaez, S. C. McQuown, G. A. Rogge et al., “HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 7, pp. 2647–2652, 2013. View at Publisher · View at Google Scholar · View at Scopus
  56. F. Santoro, O. A. Botrugno, R. Dal Zuffo et al., “A dual role for Hdac1: oncosuppressor in tumorigenesis, oncogene in tumor maintenance,” Blood, vol. 121, no. 17, pp. 3459–3468, 2013. View at Publisher · View at Google Scholar · View at Scopus
  57. Y. Komatsu, K. Tomizaki, M. Tsukamoto et al., “Cyclic hydroxamic-acid-containing peptide 31, a potent synthetic histone deacetylase inhibitor with antitumor activity,” Cancer Research, vol. 61, no. 11, pp. 4459–4466, 2001. View at Google Scholar · View at Scopus
  58. R. Soriano-Cantón, A. Perez-Villalba, J. M. Morante-Redolat et al., “Regulation of the p19Arf/p53 pathway by histone acetylation underlies neural stem cell behavior in senescence-prone SAMP8 mice,” Aging Cell, vol. 14, no. 3, pp. 453–462, 2015. View at Publisher · View at Google Scholar
  59. F. Li, R. Wu, X. Cui et al., “Histone deacetylase 1 (HDAC1) negatively regulates thermogenic program in brown adipocytes via coordinated regulation of histone H3 lysine 27 (H3K27) deacetylation and methylation,” The Journal of Biological Chemistry, vol. 291, no. 9, pp. 4523–4536, 2016. View at Publisher · View at Google Scholar
  60. K. Saijo, J. Imamura, K. Narita et al., “Biochemical, biological and structural properties of romidepsin (FK228) and its analogs as novel HDAC/PI3K dual inhibitors,” Cancer Science, vol. 106, no. 2, pp. 208–215, 2015. View at Publisher · View at Google Scholar · View at Scopus
  61. K. Sugita, H. Yoshida, M. Matsumoto, and S. Matsutani, “A novel compound, depudecin, induces production of transformation to the flat phenotype of NIH3T3 cells transformed by ras-oncogene,” Biochemical and Biophysical Research Communications, vol. 182, no. 1, pp. 379–387, 1992. View at Publisher · View at Google Scholar · View at Scopus
  62. C. Choudhary, B. T. Weinert, Y. Nishida, E. Verdin, and M. Mann, “The growing landscape of lysine acetylation links metabolism and cell signalling,” Nature Reviews Molecular Cell Biology, vol. 15, no. 8, pp. 536–550, 2014. View at Publisher · View at Google Scholar · View at Scopus
  63. M. R. Davis, J. J. Daggett, A. S. Pascual et al., “Epigenetically maintained SW13+ and SW13− subtypes have different oncogenic potential and convert with HDAC1 inhibition,” BMC Cancer, vol. 16, no. 1, pp. 1–13, 2016. View at Publisher · View at Google Scholar
  64. P.-H. Huang, C.-H. Chen, C.-C. Chou et al., “Histone deacetylase inhibitors stimulate histone H3 lysine 4 methylation in part via transcriptional repression of histone H3 lysine 4 demethylases,” Molecular Pharmacology, vol. 79, no. 1, pp. 197–206, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. J. A. Halsall, N. Turan, M. Wiersma, and B. M. Turner, “Cells adapt to the epigenomic disruption caused by histone deacetylase inhibitors through a coordinated, chromatin-mediated transcriptional response,” Epigenetics and Chromatin, vol. 8, article 29, 2015. View at Publisher · View at Google Scholar · View at Scopus
  66. W. Gu and R. G. Roeder, “Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain,” Cell, vol. 90, no. 4, pp. 595–606, 1997. View at Publisher · View at Google Scholar · View at Scopus
  67. J. Luo, M. Li, Y. Tang, M. Laszkowska, R. G. Roeder, and W. Gu, “Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 8, pp. 2259–2264, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. Y. Xu, “Regulation of p53 responses by post-translational modifications,” Cell Death and Differentiation, vol. 10, no. 4, pp. 400–403, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. A. Ito, Y. Kawaguchi, C.-H. Lai et al., “MDM2-HDAC1mediated deacetylation of p53 is required for its degradation,” The EMBO Journal, vol. 21, no. 22, pp. 6236–6245, 2002. View at Publisher · View at Google Scholar · View at Scopus
  70. Y.-H. Jin, E.-J. Jeon, Q.-L. Li et al., “Transforming growth factor-β stimulates p300-dependent RUNX3 acetylation, which inhibits ubiquitination-mediated degradation,” Journal of Biological Chemistry, vol. 279, no. 28, pp. 29409–29417, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. Z.-L. Yuan, Y.-J. Guan, D. Chatterjee, and Y. E. Chin, “Stat3 dimerization regulated by reversible acetylation of a single lysine residue,” Science, vol. 307, no. 5707, pp. 269–273, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. R. Wang, P. Cherukuri, and J. Luo, “Activation of Stat3 sequence-specific DNA binding and transcription by p300/CREB-binding protein-mediated acetylation,” The Journal of Biological Chemistry, vol. 280, no. 12, pp. 11528–11534, 2005. View at Publisher · View at Google Scholar · View at Scopus
  73. Y. Li, X. Zhang, R. D. Polakiewicz, T.-P. Yao, and M. J. Comb, “HDAC6 is required for epidermal growth factor-induced β-catenin nuclear localization,” The Journal of Biological Chemistry, vol. 283, no. 19, pp. 12686–12690, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. C. Wang, M. Fu, R. H. Angeletti et al., “Direct acetylation of the estrogen receptor α hinge region by p300 regulates transactivation and hormone sensitivity,” Journal of Biological Chemistry, vol. 276, no. 21, pp. 18375–18383, 2001. View at Publisher · View at Google Scholar · View at Scopus
  75. H. Kawai, H. Li, S. Avraham, S. Jiang, and H. K. Avraham, “Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor α,” International Journal of Cancer, vol. 107, no. 3, pp. 353–358, 2003. View at Publisher · View at Google Scholar · View at Scopus
  76. J. H. Patel, Y. Du, P. G. Ard et al., “The c-MYC oncoprotein is a substrate of the acetyltransferases hGCN5/PCAF and TIP60,” Molecular and Cellular Biology, vol. 24, no. 24, pp. 10826–10834, 2004. View at Publisher · View at Google Scholar · View at Scopus
  77. S. E. Salghetti, M. Muratani, H. Wijnen, B. Futcher, and W. P. Tansey, “Functional overlap of sequences that activate transcription and signal ubiquitin-mediated proteolysis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 7, pp. 3118–3123, 2000. View at Publisher · View at Google Scholar · View at Scopus
  78. W. Zhang, S. Kadam, B. M. Emerson, and J. J. Bieker, “Site-specific acetylation by p300 or CREB binding protein regulates erythroid Krüppel-like factor transcriptional activity via its interaction with the SWI-SNF complex,” Molecular and Cellular Biology, vol. 21, no. 7, pp. 2413–2422, 2001. View at Publisher · View at Google Scholar · View at Scopus
  79. W. Zhang and J. J. Bieker, “Acetylation and modulation of erythroid Krüppel-like factor (EKLF) activity by interaction with histone acetyltransferases,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 17, pp. 9855–9860, 1998. View at Publisher · View at Google Scholar · View at Scopus
  80. M. A. Martínez-Balbás, U.-M. Bauer, S. J. Nielsen, A. Brehm, and T. Kouzarides, “Regulation of E2F1 activity by acetylation,” The EMBO Journal, vol. 19, no. 4, pp. 662–671, 2000. View at Publisher · View at Google Scholar · View at Scopus
  81. G. Marzio, C. Wagener, M. I. Gutierrez, P. Cartwright, K. Helin, and M. Giacca, “E2F family members are differentially regulated by reversible acetylation,” The Journal of Biological Chemistry, vol. 275, no. 15, pp. 10887–10892, 2000. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Boyes, P. Byfield, Y. Nakatani, and V. Ogryzko, “Regulation of activity of the transcription factor GATA-1 by acetylation,” Nature, vol. 396, no. 6711, pp. 594–598, 1998. View at Publisher · View at Google Scholar · View at Scopus
  83. F. Hayakawa, M. Towatari, Y. Ozawa, A. Tomita, M. L. Privalsky, and H. Saito, “Functional regulation of GATA-2 by acetylation,” Journal of Leukocyte Biology, vol. 75, no. 3, pp. 529–540, 2004. View at Publisher · View at Google Scholar · View at Scopus
  84. T. Yamagata, K. Mitani, H. Oda et al., “Acetylation of GATA-3 affects T-cell survival and homing to secondary lymphoid organs,” The EMBO Journal, vol. 19, no. 17, pp. 4676–4687, 2000. View at Publisher · View at Google Scholar · View at Scopus
  85. J.-W. Jeong, M.-K. Bae, M.-Y. Ahn et al., “Regulation and destabilization of HIF-1α by ARD1-mediated acetylation,” Cell, vol. 111, no. 5, pp. 709–720, 2002. View at Publisher · View at Google Scholar · View at Scopus
  86. V. Sartorelli, P. L. Puri, Y. Hamamori et al., “Acetylation of MyoD directed by PCAF is necessary for the execution of the muscle program,” Molecular Cell, vol. 4, no. 5, pp. 725–734, 1999. View at Publisher · View at Google Scholar · View at Scopus
  87. A. Polesskaya and A. Harel-Bellan, “Acetylation of MyoD by p300 requires more than its histone acetyltransferase domain,” The Journal of Biological Chemistry, vol. 276, no. 48, pp. 44502–44503, 2001. View at Publisher · View at Google Scholar · View at Scopus
  88. A. Polesskaya, A. Duquet, I. Naguibneva et al., “CREB-binding protein/p300 activates MyoD by acetylation,” The Journal of Biological Chemistry, vol. 275, no. 44, pp. 34359–34364, 2000. View at Publisher · View at Google Scholar · View at Scopus
  89. L.-F. Chen, W. Fischle, E. Verdin, and W. C. Greene, “Duration of nuclear NF-κB action regulated by reversible acetylation,” Science, vol. 293, no. 5535, pp. 1653–1657, 2001. View at Publisher · View at Google Scholar · View at Scopus
  90. H.-S. Kwon, H. W. Lim, J. Wu, M. Schnölzer, E. Verdin, and M. Ott, “Three novel acetylation sites in the Foxp3 transcription factor regulate the suppressive activity of regulatory T cells,” Journal of Immunology, vol. 188, no. 6, pp. 2712–2721, 2012. View at Publisher · View at Google Scholar · View at Scopus
  91. Q. Cao, J. Yu, S. M. Dhanasekaran et al., “Repression of E-cadherin by the polycomb group protein EZH2 in cancer,” Oncogene, vol. 27, no. 58, pp. 7274–7284, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. S. Glaros, G. M. Cirrincione, C. Muchardt, C. G. Kleer, C. W. Michael, and D. Reisman, “The reversible epigenetic silencing of BRM: implications for clinical targeted therapy,” Oncogene, vol. 26, no. 49, pp. 7058–7066, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. N. Yamamichi, M. Yamamichi-Nishina, T. Mizutani et al., “The Brm gene suppressed at the post-transcriptional level in various human cell lines is inducible by transient HDAC inhibitor treatment, which exhibits antioncogenic potential,” Oncogene, vol. 24, no. 35, pp. 5471–5481, 2005. View at Publisher · View at Google Scholar · View at Scopus
  94. C. Kadoch, D. C. Hargreaves, C. Hodges et al., “Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy,” Nature Genetics, vol. 45, no. 6, pp. 592–601, 2013. View at Publisher · View at Google Scholar · View at Scopus
  95. Y. Y. Sanders, T. O. Tollefsbol, B. M. Varisco, and J. S. Hagood, “Epigenetic regulation of Thy-1 by histone deacetylase inhibitor in rat lung fibroblasts,” American Journal of Respiratory Cell and Molecular Biology, vol. 45, no. 1, pp. 16–23, 2011. View at Publisher · View at Google Scholar · View at Scopus
  96. H. Jia, C. D. Morris, R. M. Williams, J. F. Loring, and E. A. Thomas, “HDAC inhibition imparts beneficial transgenerational effects in Huntington's disease mice via altered DNA and histone methylation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 1, pp. E56–E64, 2015. View at Publisher · View at Google Scholar · View at Scopus
  97. T. Wada, J. Kikuchi, and Y. Furukawa, “Histone deacetylase 1 enhances microRNA processing via deacetylation of DGCR8,” EMBO Reports, vol. 13, no. 2, pp. 142–149, 2012. View at Publisher · View at Google Scholar · View at Scopus
  98. E. J. Noonan, R. F. Place, D. Pookot et al., “MiR-449a targets HDAC-1 and induces growth arrest in prostate cancer,” Oncogene, vol. 28, no. 14, pp. 1714–1724, 2009. View at Publisher · View at Google Scholar · View at Scopus
  99. H. J. Bae, K. H. Jung, J. W. Eun et al., “MicroRNA-221 governs tumor suppressor HDAC6 to potentiate malignant progression of liver cancer,” Journal of Hepatology, vol. 63, no. 2, pp. 408–419, 2015. View at Publisher · View at Google Scholar · View at Scopus
  100. T. Qiu, L. Zhou, W. Zhu et al., “Effects of treatment with histone deacetylase inhibitors in solid tumors: a review based on 30 clinical trials,” Future Oncology, vol. 9, no. 2, pp. 255–269, 2013. View at Publisher · View at Google Scholar · View at Scopus
  101. M. Slingerland, H.-J. Guchelaar, and H. Gelderblom, “Histone deacetylase inhibitors: an overview of the clinical studies in solid tumors,” Anti-Cancer Drugs, vol. 25, no. 2, pp. 140–149, 2014. View at Publisher · View at Google Scholar · View at Scopus
  102. N. Ahuja, H. Easwaran, and S. B. Baylin, “Harnessing the potential of epigenetic therapy to target solid tumors,” The Journal of Clinical Investigation, vol. 124, no. 1, pp. 56–63, 2014. View at Publisher · View at Google Scholar · View at Scopus
  103. L. Andresen, H. Jensen, M. T. Pedersen, K. A. Hansen, and S. Skov, “Molecular regulation of MHC class I chain-related protein A expression after HDAC-inhibitor treatment of jurkat T cells,” The Journal of Immunology, vol. 179, no. 12, pp. 8235–8242, 2007. View at Publisher · View at Google Scholar · View at Scopus
  104. J. S. Waby, H. Chirakkal, C. Yu et al., “Sp1 acetylation is associated with loss of DNA binding at promoters associated with cell cycle arrest and cell death in a colon cell line,” Molecular Cancer, vol. 9, article 275, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. M. D. Cantley, D. P. Fairlie, P. M. Bartold, V. Marino, P. K. Gupta, and D. R. Haynes, “Inhibiting histone deacetylase 1 suppresses both inflammation and bone loss in arthritis,” Rheumatology, vol. 54, no. 9, pp. 1713–1723, 2015. View at Publisher · View at Google Scholar · View at Scopus
  106. N. Mishra, C. M. Reilly, D. R. Brown, P. Ruiz, and G. S. Gilkeson, “Histone deacetylase inhibitors modulate renal disease in the MRL-lpr/lpr mouse,” The Journal of Clinical Investigation, vol. 111, no. 4, pp. 539–552, 2003. View at Publisher · View at Google Scholar · View at Scopus
  107. N. Mishra, D. R. Brown, I. M. Olorenshaw, and G. M. Kammer, “Trichostatin A reverses skewed expression of CD154, interleukin-10, and interferon-γ gene and protein expression in lupus T cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 5, pp. 2628–2633, 2001. View at Publisher · View at Google Scholar · View at Scopus
  108. X. Wu, Y. Tao, J. Hou, X. Meng, and J. Shi, “Valproic acid upregulates NKG2D ligand expression through an ERK-dependent mechanism and potentially enhances NK cell-mediated lysis of myeloma,” Neoplasia, vol. 14, no. 12, pp. 1178–1189, 2012. View at Publisher · View at Google Scholar · View at Scopus
  109. S. Armeanu, M. Bitzer, U. M. Lauer et al., “Natural killer cell-mediated lysis of hepatoma cells via specific induction of NKG2D ligands by the histone deacetylase inhibitor sodium valproate,” Cancer Research, vol. 65, no. 14, pp. 6321–6329, 2005. View at Publisher · View at Google Scholar · View at Scopus
  110. D. M. Woods, A. L. Sodre, A. Villagra, A. Sarnaik, E. M. Sotomayor, and J. Weber, “HDAC inhibition upregulates PD-1 ligands in melanoma and augments immunotherapy with PD-1 blockade,” Cancer Immunology Research, vol. 3, no. 12, pp. 1375–1385, 2015. View at Publisher · View at Google Scholar
  111. S. Skov, M. T. Pedersen, L. Andresen, P. T. Straten, A. Woetmann, and N. Ødum, “Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B,” Cancer Research, vol. 65, no. 23, pp. 11136–11145, 2005. View at Publisher · View at Google Scholar · View at Scopus
  112. K. V. Woan, M. Lienlaf, P. Perez-Villaroel et al., “Targeting histone deacetylase 6 mediates a dual anti-melanoma effect: enhanced antitumor immunity and impaired cell proliferation,” Molecular Oncology, vol. 9, no. 7, pp. 1447–1457, 2015. View at Publisher · View at Google Scholar · View at Scopus
  113. J. Manning, M. Indrova, B. Lubyova et al., “Induction of MHC class I molecule cell surface expression and epigenetic activation of antigen-processing machinery components in a murine model for human papilloma virus 16-associated tumours,” Immunology, vol. 123, no. 2, pp. 218–227, 2008. View at Publisher · View at Google Scholar · View at Scopus
  114. D. M. Woods, K. Woan, F. Cheng et al., “The antimelanoma activity of the histone deacetylase inhibitor panobinostat (LBH589) is mediated by direct tumor cytotoxicity and increased tumor immunogenicity,” Melanoma Research, vol. 23, no. 5, pp. 341–348, 2013. View at Publisher · View at Google Scholar · View at Scopus
  115. R. Di Liddo, S. Valente, S. Taurone et al., “Histone deacetylase inhibitors restore IL-10 expression in lipopolysaccharide-induced cell inflammation and reduce IL-1β and IL-6 production in breast silicone implant in C57BL/6J wild-type murine model,” Autoimmunity, 2016. View at Publisher · View at Google Scholar · View at Scopus
  116. F. Cheng, M. Lienlaf, P. Perez-Villarroel et al., “Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11 (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells,” Molecular Immunology, vol. 60, no. 1, pp. 44–53, 2014. View at Publisher · View at Google Scholar · View at Scopus
  117. F. Cheng, M. Lienlaf, H.-W. Wang et al., “A novel role for histone deacetylase 6 in the regulation of the tolerogenic STAT3/IL-10 pathway in APCs,” Journal of Immunology, vol. 193, no. 6, pp. 2850–2862, 2014. View at Publisher · View at Google Scholar · View at Scopus
  118. A. F. Setiadi, K. Omilusik, M. D. David et al., “Epigenetic enhancement of antigen processing and presentation promotes immune recognition of tumors,” Cancer Research, vol. 68, no. 23, pp. 9601–9607, 2008. View at Publisher · View at Google Scholar · View at Scopus
  119. I. M. Adcock, “HDAC inhibitors as anti-inflammatory agents,” British Journal of Pharmacology, vol. 150, no. 7, pp. 829–831, 2007. View at Publisher · View at Google Scholar · View at Scopus
  120. C. A. Dinarello, “Anti-inflammatory agents: present and future,” Cell, vol. 140, no. 6, pp. 935–950, 2010. View at Publisher · View at Google Scholar · View at Scopus
  121. C. A. Dinarello, G. Fossati, and P. Mascagni, “Histone deacetylase inhibitors for treating a spectrum of diseases not related to cancer,” Molecular Medicine, vol. 17, no. 5-6, pp. 333–352, 2011. View at Publisher · View at Google Scholar · View at Scopus
  122. A. J. P. Edwards and S. L. F. Pender, “Histone deacetylase inhibitors and their potential role in inflammatory bowel diseases,” Biochemical Society Transactions, vol. 39, no. 4, pp. 1092–1095, 2011. View at Publisher · View at Google Scholar · View at Scopus
  123. W. W. Hancock, T. Akimova, U. H. Beier, Y. Liu, and L. Wang, “HDAC inhibitor therapy in autoimmunity and transplantation,” Annals of the Rheumatic Diseases, vol. 71, supplement 2, pp. i46–i54, 2012. View at Publisher · View at Google Scholar · View at Scopus
  124. B. W. Bridle, L. Chen, C. G. Lemay et al., “HDAC inhibition suppresses primary immune responses, enhances secondary immune responses, and abrogates autoimmunity during tumor immunotherapy,” Molecular Therapy, vol. 21, no. 4, pp. 887–894, 2013. View at Publisher · View at Google Scholar · View at Scopus
  125. L. Larsen, M. Tonnesen, S. G. Ronn et al., “Inhibition of histone deacetylases prevents cytokine-induced toxicity in beta cells,” Diabetologia, vol. 50, no. 4, pp. 779–789, 2007. View at Publisher · View at Google Scholar · View at Scopus
  126. S. J. Shuttleworth, S. G. Bailey, and P. A. Townsend, “Histone Deacetylase inhibitors: new promise in the treatment of immune and inflammatory diseases,” Current Drug Targets, vol. 11, no. 11, pp. 1430–1438, 2010. View at Publisher · View at Google Scholar · View at Scopus
  127. G. Faraco, L. Cavone, and A. Chiarugi, “The therapeutic potential of HDAC inhibitors in the treatment of multiple sclerosis,” Molecular Medicine, vol. 17, no. 5-6, pp. 442–447, 2011. View at Publisher · View at Google Scholar · View at Scopus
  128. S. Camelo, A. H. Iglesias, D. Hwang et al., “Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis,” Journal of Neuroimmunology, vol. 164, no. 1-2, pp. 10–21, 2005. View at Publisher · View at Google Scholar · View at Scopus
  129. A. S. Fiorino and I. Zvibel, “Disruption of cell-cell adhesion in the presence of sodium butyrate activates expression of the 92 kDa type IV collagenase in MDCK cells,” Cell Biology International, vol. 20, no. 7, pp. 489–499, 1996. View at Publisher · View at Google Scholar · View at Scopus
  130. M. J. LaBonte, P. M. Wilson, W. Fazzone, S. Groshen, H.-J. Lenz, and R. D. Ladner, “DNA microarray profiling of genes differentially regulated by the histone deacetylase inhibitors vorinostat and LBH589 in colon cancer cell lines,” BMC Medical Genomics, vol. 2, article 67, 2009. View at Publisher · View at Google Scholar · View at Scopus
  131. E. Bandres, X. Agirre, N. Bitarte et al., “Epigenetic regulation of microRNA expression in colorectal cancer,” International Journal of Cancer, vol. 125, no. 11, pp. 2737–2743, 2009. View at Publisher · View at Google Scholar · View at Scopus
  132. S. Diederichs and D. A. Haber, “Sequence variations of microRNAs in human cancer: alterations in predicted secondary structure do not affect processing,” Cancer Research, vol. 66, no. 12, pp. 6097–6104, 2006. View at Publisher · View at Google Scholar · View at Scopus
  133. K.-T. Lin, Y.-W. Wang, C.-T. Chen, C.-M. Ho, W.-H. Su, and Y.-S. Jou, “HDAC inhibitors augmented cell migration and metastasis through induction of PKCs leading to identification of low toxicity modalities for combination cancer therapy,” Clinical Cancer Research, vol. 18, no. 17, pp. 4691–4701, 2012. View at Publisher · View at Google Scholar · View at Scopus
  134. E. Benito, H. Urbanke, B. Ramachandran et al., “HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models,” Journal of Clinical Investigation, vol. 125, no. 9, pp. 3572–3584, 2015. View at Publisher · View at Google Scholar · View at Scopus
  135. A. S. Sewal, H. Patzke, E. J. Perez et al., “Experience modulates the effects of histone deacetylase inhibitors on gene and protein expression in the hippocampus: impaired plasticity in aging,” The Journal of Neuroscience, vol. 35, no. 33, pp. 11729–11742, 2015. View at Publisher · View at Google Scholar · View at Scopus
  136. S. Aslibekyan, E. W. Demerath, M. Mendelson et al., “Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference,” Obesity, vol. 23, no. 7, pp. 1493–1501, 2015. View at Publisher · View at Google Scholar · View at Scopus
  137. S. Keleg, P. Büchler, R. Ludwig, M. W. Büchler, and H. Friess, “Invasion and metastasis in pancreatic cancer,” Molecular Cancer, vol. 2, article 14, 2003. View at Publisher · View at Google Scholar · View at Scopus
  138. L. Robert, A. Ribas, and S. Hu-Lieskovan, “Combining targeted therapy with immunotherapy. Can 1+1 equal more than 2?” Seminars in Immunology, vol. 28, no. 1, pp. 73–80, 2016. View at Publisher · View at Google Scholar
  139. S. S. Ramalingam, M. L. Maitland, P. Frankel et al., “Carboplatin and paclitaxel in combination with either vorinostat or placebo for first-line therapy of advanced non-small-cell lung cancer,” Journal of Clinical Oncology, vol. 28, no. 1, pp. 56–62, 2010. View at Publisher · View at Google Scholar · View at Scopus
  140. D. A. Yardley, R. R. Ismail-Khan, B. Melichar et al., “Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor,” Journal of Clinical Oncology, vol. 31, no. 17, pp. 2128–2135, 2013. View at Publisher · View at Google Scholar · View at Scopus
  141. M. Balliu, L. Guandalini, M. N. Romanelli, M. D'Amico, and F. Paoletti, “HDAC-inhibitor (S)-8 disrupts HDAC6-PP1 complex prompting A375 melanoma cell growth arrest and apoptosis,” Journal of Cellular and Molecular Medicine, vol. 19, no. 1, pp. 143–154, 2015. View at Publisher · View at Google Scholar · View at Scopus
  142. L. Shen, A. Orillion, and R. Pili, “Histone deacetylase inhibitors as immunomodulators in cancer therapeutics,” Epigenomics, vol. 8, no. 3, pp. 415–428, 2016. View at Publisher · View at Google Scholar