Recovery of Genes Epigenetically Altered by the Histone Deacetylase Inhibitor Scriptaid and Demethylating Agent 5-Azacytidine in Human Leukemia Cells.

Park,  Eunkyung; Jeon,  Eunhyung; Kim,  In Ho; Park,  Seonyang

doi:2010.8.4.185

Genomics Inform > Volume 8(4); 2010 > Article

Original Article

Genomics & Informatics 2010;8(4): 185-193.

DOI: https://doi.org/10.5808/gi.2010.8.4.185

Recovery of Genes Epigenetically Altered by the Histone Deacetylase Inhibitor Scriptaid and Demethylating Agent 5-Azacytidine in Human Leukemia Cells.

Eunkyung Park, Eunhyung Jeon, In Ho Kim, Seonyang Park

¹Diagnostic DNA Chip Center, Seoul National University College of Medicine, Seoul, Korea. seonpark@plaza.snu.ac.kr
²Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 156-755, Korea.
³Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Korea.

Abstract

Histone deacetylation and demethylation are epigenetic mechanisms implicated in cancer. Studies regarding the role of modulation of gene expression utilizing the histone deacetylase inhibitor scriptaid and the demethylating agent 5-azacytidine in HL-60 leukemia cells have been limited. We studied the possibility of recovering epigenetically silenced genes by scriptaid and 5-azacytidine in human leukemia cells by DNA microarray analysis. The first group was leukemia cells that were cultured with 5-azacytidine. The second group was cultured with scriptaid. The other group was cultured with both agents. Two hundred seventy newly developed genes were expressed after the combination of 5-azacytidine and scriptaid. Twenty-nine genes were unchanged after the combination treatment of 5-azacytidine and scriptaid. Among the 270 genes, 13 genes were differed significantly from the control. HPGD , CPA3, CEACAM6, LOC653907, ETS1, RAB37, PMP22, FST, FOXC1, and CCL2 were up-regulated, and IGLL3, IGLL1, and ASS1 were down-regulated. Eleven genes associated with oncogenesis were found among the differentially expressed genes: ETS1, ASCL2, BTG2, BTG1, SLAMF6, CDKN2D, RRAS, RET, GIPC1, MAGEB, and RGL4. We report the results of our leukemia cell microarray profiles after epigenetic combination therapy with the hope that they are the starting point of selectively targeted epigenetic therapy.

Keywords: deacetylation; demethylation; epigenetic; leukemia; microarray