Targeted demethylation at ZNF154 promotor upregulates ZNF154 expression and inhibits the proliferation and migration of Esophageal Squamous Carcinoma cells

Zinc finger protein 154 (ZNF154) is hypermethylated at the promoter in many epithelial-derived solid tumors. However, its methylation status and function in esophageal squamous carcinoma (ESCC) are poorly understood. We found that the ZNF154 promoter is hypermethylated in ESCC and portends poor prog...

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Published in:Oncogene 2022-09, Vol.41 (40), p.4537-4546
Main Authors: He, Wenting, Lin, Shiyong, Guo, Yi, Wu, Yuanzhong, Zhang, Lu-Lu, Deng, Qiling, Du, Zi-Ming, Wei, Mingbiao, Zhu, Weijie, Chen, Wan-Juan, Shao, Jian-Yong, Xu, Guo-Liang
Format: Article
Language:English
Subjects:
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Apoptosis
Cell Biology
Cell migration
Cell proliferation
CRISPR
Demethylation
DNA methylation
Epigenetics
Esophageal cancer
Esophagus
Human Genetics
Internal Medicine
Medicine
Medicine & Public Health
Oncology
Solid tumors
Tumor suppressor genes
Zinc finger proteins
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Summary:Zinc finger protein 154 (ZNF154) is hypermethylated at the promoter in many epithelial-derived solid tumors. However, its methylation status and function in esophageal squamous carcinoma (ESCC) are poorly understood. We found that the ZNF154 promoter is hypermethylated in ESCC and portends poor prognosis. In addition, ZNF154 functions as a tumor suppressor gene (TSG) in ESCC, and is downregulated by promoter hypermethylation. We established a targeted demethylation strategy based on CRISPR/dCas9 technology and found that the hypermethylation of ZNF154 promoter repressed ZNF154 induction, which in turn promoted the proliferation and migration of ESCC cells in vitro and in vivo. Finally, high-throughput CUT&Tag analysis, GEPIA software and qPCR were used to revealed the role of ZNF154 as a transcription factor to upregulate the expression of ESCC-associated tumor suppressor genes. Taken together, hypermethylation of the ZNF154 promoter plays an important role in the development of ESCC, and epigenetic editing is a promising tool for inhibiting ESCC cells with aberrant DNA methylation.
ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-022-02366-y