The novel 19q13 KRAB zinc-finger tumour suppressor ZNF382 is frequently methylated in oesophageal squamous cell carcinoma and antagonises Wnt/β-catenin signalling

Cell Death & Disease
Chong ZhangQian Tao

Abstract

Zinc finger proteins (ZFPs) are the largest transcription factor family in mammals. About one-third of ZFPs are Krüppel-associated box domain (KRAB)-ZFPs and involved in the regulation of cell differentiation/proliferation/apoptosis and neoplastic transformation. We recently identified ZNF382 as a novel KRAB-ZFP epigenetically inactivated in multiple cancers due to frequent promoter CpG methylation. However, its epigenetic alterations, biological functions/mechanism and clinical significance in oesophageal squamous cell carcinoma (ESCC) are still unknown. Here, we demonstrate that ZNF382 expression was suppressed in ESCC due to aberrant promoter methylation, but highly expressed in normal oesophagus tissues. ZNF382 promoter methylation is correlated with ESCC differentiation levels. Restoration of ZNF382 expression in silenced ESCC cells suppressed tumour cell proliferation and metastasis through inducing cell apoptosis. Importantly, ZNF382 suppressed Wnt/β-catenin signalling and downstream target gene expression, likely through binding directly to FZD1 and DVL2 promoters. In summary, our findings demonstrate that ZNF382 functions as a bona fide tumour suppressor inhibiting ESCC pathogenesis through inhibiting the Wnt/β-catenin...Continue Reading

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Citations

Nov 5, 2019·Clinica Chimica Acta; International Journal of Clinical Chemistry·Shi ChenXi Zeng
Mar 7, 2021·International Journal of Molecular Sciences·Joanna SobocińskaUrszula Oleksiewicz

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Methods Mentioned

BETA
PCR
transfection
flow cytometry
transfections
RNA-Seq
ChIP-Seq
electrophoresis
phase contrast microscopy
Assay
immunoprecipitation

Software Mentioned

bigWig
scienceslides
Cytoscape
BEDTools
Integrated Genomics Viewer
DESeq

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