In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 4326-4326
Kurzfassung:
Gastric cancer is one of the most common causes of cancer death worldwide. Aberrant activation of JAK/STAT3 signaling is frequently observed in gastric cancer and associated with cancer progression. Our previous studies demonstrated that several STAT3 targets and tumor suppressors such as NR4A3 and GATA6 are found to be epigenetically silenced by DNA methylation in gastric cancer. However, the role of aberrant JAK/STAT3 signaling in the epigenetic changes of downstream targets is not fully understood. In this study, by using Methylation EPIC array, we compared the global methylation changes in gastric cancer patient samples with different STAT3 activation level. In silico analysis was also performed to identify STAT3 binding sites in those differentially methylated loci. Hypermethylated loci which are functionally relate carcinogenesis and mediated by STAT3 expression were examined. Interestingly, SMARCAL1, which was involved in chromosome stability and alternative lengthening of telomeres was identified. Unexpectedly, differentially methylated region (DMR) was not occurred in the promoter, but enhancer region located in the CpG island shore. Additionally, we also found a transcription factor binding site, YY1, which was a methylation-sensitive enhancer-promoter regulator, in this DMR region. By using a statistic shuffling model, we found that STAT3 related methylation changes were significantly associated with H3K4me1 and H3K27me3 at that region. TCGA dataset also indicated that this DMR with dramatic changes was occurred in chromosome instability (CIN) subtype of gastric cancer, whereas the expression of SMARCAL1 was decreased in precancerous lesion in previous published data. Taken together, STAT3-related methylation changes may regulate the activity of enhancer and affect the expression of SMARCAL1, during gastric cancer progression. Citation Format: Yu Ming Chuang, Sheng-Jou Hung, Jiang Liang Chou, Wan-Hong Huang, Pearlly S. Yan, Tsunglin Liu, Michael W.Y. Chan. Epigenetic control of chromosome instability by STAT3 in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4326.
Materialart:
Online-Ressource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2019-4326
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2019
ZDB Id:
2036785-5
ZDB Id:
1432-1
ZDB Id:
410466-3
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