ZIC1 is downregulated through promoter hypermethylation in gastric cancer

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Liang Jing Wang
  • Hong Chuan Jin
  • Xian Wang
  • Emily K.Y. Lam
  • Jian Bin Zhang
  • And 4 others
  • Xin Liu
  • Francis K.L. Chan
  • Jian Min Si
  • Joseph J.Y. Sung

Detail(s)

Original languageEnglish
Pages (from-to)959-963
Journal / PublicationBiochemical and Biophysical Research Communications
Volume379
Issue number4
Publication statusPublished - 20 Feb 2009

Abstract

As one of major epigenetic changes responsible for tumor suppressor gene inactivation in the development of cancer, promoter hypermethylation was proposed as a marker to define novel tumor suppressor genes. In the current study we identified ZIC1 (Zic family member 1, odd-paired Drosophila homolog) as a novel tumor suppressor gene silenced through promoter hypermethylation in gastric cancer, the second leading cause of cancer death worldwide. In all of gastric cancer cells lines examined, ZIC1 expression was downregulated and such downregulation was accompanied with the hypermethylation of ZIC1 promoter. Demethylation treatment with 5-aza-2′-deoxycytidine (Aza) reversed ZIC1 downregulation, highlighting the importance of promoter methylation to ZIC1 downregulation in gastric cancer cells. Notably, ZIC1 expression was significantly downregulated in primary gastric carcinoma tissues in comparison with non-tumor adjacent gastric tissues (p <0.01). Accordingly, promoter methylation of ZIC1 was frequently detected in primary gastric carcinoma tissues (94.6%, 35/37) but not normal gastric tissues, indicating that promoter hypermethylation mediated ZIC1 downregulation may play an important role in gastric carcinogenesis. Indeed, ectopic expression of ZIC1 led to the growth inhibition of gastric cancer cells through the induction of S-phase cell cycle arrest (p <0.01). Our results revealed ZIC1 as a novel candidate tumor suppressor gene downregulated through promoter hypermethylation in gastric cancer. © 2009 Elsevier Inc. All rights reserved.

Research Area(s)

  • Gastric cancer, Methylation, Tumor suppressor gene, ZIC1

Citation Format(s)

ZIC1 is downregulated through promoter hypermethylation in gastric cancer. / Wang, Liang Jing; Jin, Hong Chuan; Wang, Xian; Lam, Emily K.Y.; Zhang, Jian Bin; Liu, Xin; Chan, Francis K.L.; Si, Jian Min; Sung, Joseph J.Y.

In: Biochemical and Biophysical Research Communications, Vol. 379, No. 4, 20.02.2009, p. 959-963.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review