The interplay between histone deacetylases and c-Myc in the transcriptional suppression of HPP1 in colon cancer

Jian Wang, Abul Elahi, Abidemi Ajidahun, Whalen Clark, Jonathan Hernandez, Alex Achille, Ji Hui Hao, Edward Seto, David Shibata

Research output: Contribution to journalArticle

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Abstract

HPP1 (hyperplastic polyposis protein 1), a tumor suppressor gene, is downregulated by promoter hypermethylation in a number of tumor types including colon cancer. c-Myc is also known to play a role in the suppression of HPP1 expression via binding to a promoter region cognate E-box site. The contribution of histone deacetylation as an additional epigenetic mechanism and its potential interplay with c-Myc in the transcriptional regulation of HPP1 are unknown. We have shown that the treatment of the HPP1-non-expressing colon cancer cell lines, HCT116 and DLD-1 with HDAC inhibitors results in re-expression of HPP1. RNAi-mediated knockdown of c-Myc as well as of HDAC2 and HDAC3 in HCT116 and of HDAC1 and HDAC3 in DLD-1 also resulted in significant re-expression of HPP1. Co-immunoprecipitation (IP), chromatin IP (ChIP), and sequential ChIP experiments demonstrated binding of c-Myc to the HPP1 promoter with recruitment of and direct interaction with HDAC3. In summary, we have demonstrated that c-Myc contributes to the epigenetic regulation of HPP1 via the dominant recruitment of HDAC3. Our findings may lead to a greater biologic understanding for the application of targeted use of HDAC inhibitors for anti-cancer therapy.

Original languageEnglish (US)
Pages (from-to)1198-1207
Number of pages10
JournalCancer Biology and Therapy
Volume15
Issue number9
DOIs
StatePublished - Jan 1 2014

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Histone Deacetylases
Colonic Neoplasms
Proteins
Histone Deacetylase Inhibitors
Immunoprecipitation
Epigenomics
E-Box Elements
Chromatin Immunoprecipitation
RNA Interference
Tumor Suppressor Genes
Genetic Promoter Regions
Histones
Chromatin
Neoplasms
Down-Regulation
Cell Line

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

The interplay between histone deacetylases and c-Myc in the transcriptional suppression of HPP1 in colon cancer. / Wang, Jian; Elahi, Abul; Ajidahun, Abidemi; Clark, Whalen; Hernandez, Jonathan; Achille, Alex; Hao, Ji Hui; Seto, Edward; Shibata, David.

In: Cancer Biology and Therapy, Vol. 15, No. 9, 01.01.2014, p. 1198-1207.

Research output: Contribution to journalArticle

Wang, J, Elahi, A, Ajidahun, A, Clark, W, Hernandez, J, Achille, A, Hao, JH, Seto, E & Shibata, D 2014, 'The interplay between histone deacetylases and c-Myc in the transcriptional suppression of HPP1 in colon cancer', Cancer Biology and Therapy, vol. 15, no. 9, pp. 1198-1207. https://doi.org/10.4161/cbt.29500
Wang, Jian ; Elahi, Abul ; Ajidahun, Abidemi ; Clark, Whalen ; Hernandez, Jonathan ; Achille, Alex ; Hao, Ji Hui ; Seto, Edward ; Shibata, David. / The interplay between histone deacetylases and c-Myc in the transcriptional suppression of HPP1 in colon cancer. In: Cancer Biology and Therapy. 2014 ; Vol. 15, No. 9. pp. 1198-1207.
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