2. Academic Validation
  3. Epigenetic silencing of ZIC4 contributes to cancer progression in hepatocellular carcinoma

Epigenetic silencing of ZIC4 contributes to cancer progression in hepatocellular carcinoma

  • Cell Death Dis. 2020 Oct 23;11(10):906. doi: 10.1038/s41419-020-03109-1.
Wenbiao Chen 1,  Donge Tang 1,  Dongxin Tang 2,  Yong Dai 3
Affiliations

Affiliations

  • 1 Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, 518020, China.
  • 2 Department of Science and Education, The First Affiliated Hospital of Guiyang University of Chinese Medicine, Guiyang, 550001, Guizhou, China. [email protected].
  • 3 Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, 518020, China. [email protected].
PMID: 33097694 DOI: 10.1038/s41419-020-03109-1
Abstract

Inactivation of tumor suppressor gene played critical roles in the development and progression of human hepatocellular carcinoma (HCC). Zic family member 4 (ZIC4) is transcription factor and plays an important role in the developmental process. However, the expression and biological role of ZIC4 in HCC is poorly understood. Here, bioinformatics analysis based on The Cancer Genome Atlas (TCGA) database revealed an aberrant hypermethylation of ZIC4 in HCC. ZIC4 is frequently hypermethylated in promoter region and down expressed in HCC cells and tissues. Functionally, ZIC4 inhibition facilitated the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Conversely, ZIC4 overexpression reduced proliferation and invasiveness of HCC cells. In addition, ZIC4 inhibition rescued the antitumor effect induced by enhancer of zeste homolog 2 (EZH2) knockdown or EZH2 Inhibitor. Mechanistically, EZH2 knockdown or EZH2 Inhibitor reduced the enrichment of EZH2 and H3K27me3 in ZIC4 promoter region and leading to the upregulation of ZIC4. Altogether, these data indicate that epigenetic silencing of ZIC4 by EZH2 mediated H3K27me3 is an important mechanism in HCC and provide a new therapeutic target for the treatment of hepatocellular carcinoma disease.

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