Epigenetic changes induced by oxidative stress in colorectal cancer cells: methylation of tumor suppressor RUNX3

• DOI: 10.1007/s13277-012-0322-6
• Publication Date: 2012-01-24T05:36:03Z
• Authors: Kyoung Ah Kang; Rui Zhang; Gi Young Kim; Suk Chul Bae; Jin Won Hyun
• Keywords: DNMT1

Runt domain transcription factor 3 (RUNX3) is a tumor suppressor that silenced in cancer via hypermethylation of its promoter. This study investigated the mechanisms involved reactive oxygen species (ROS)-induced silencing RUNX3 terms epigenetic alteration since effects oxidative stress gene are largely unknown. mRNA and protein expressions were down-regulated response to hydrogen peroxide (H(2)O(2)) human colorectal cell line SNU-407. down-regulation was abolished with pretreatment ROS scavenger, N-acetylcysteine (NAC). Moreover, methylation-specific PCR data revealed H(2)O(2) treatment increased promoter methylation; however, NAC cytosine methylation inhibitor, 5-aza-2-deoxycytidine (5-Aza-dC), decreased it, suggesting an regulatory mechanism by ROS-induced may be silencing. resulted DNA methyltransferase 1 (DNMT1) histone deacetylase (HDAC1) up-regulation expression activity, binding DNMT1 HADC1, In addition, 5-Aza-dC prevented decrease levels treatment. Additionally, inhibited nuclear localization RUNX3, which Furthermore, also influenced proliferation. Taken together, suggested suppressor, regulation therefore associated progression cancer.