RRC ID 66855
Author Zhang L, Huo Q, Ge C, Zhao F, Zhou Q, Chen X, Tian H, Chen T, Xie H, Cui Y, Yao M, Li H, Li J.
Title ZNF143-Mediated H3K9 Trimethylation Upregulates CDC6 by Activating MDIG in Hepatocellular Carcinoma.
Journal Cancer Res
Abstract Zinc finger protein 143 (ZNF143) belongs to the zinc finger protein family and possesses transcription factor activity by binding sequence-specific DNA. The exact biological role of ZNF143 in hepatocellular carcinoma (HCC) has not been investigated. Here we report that ZNF143 is overexpressed in HCC tissues and its overexpression correlates with poor prognosis. Gain- and loss-of-function experiments showed that ZNF143 promoted HCC cell proliferation, colony formation, and tumor growth in vitro and in vivo. ZNF143 accelerated HCC cell-cycle progression by activating cell division cycle 6 (CDC6). Mechanistically, ZNF143 promoted expression of CDC6 by directly activating transcription of histone demethylase mineral dust-induced gene (MDIG), which in turn reduced H3K9me3 enrichment in the CDC6 promoter region. Consistently, ZNF143 expression correlated significantly with MDIG and CDC6 expression in HCC. Collectively, we propose a model for a ZNF143-MDIG-CDC6 oncoprotein axis that provides novel insight into ZNF143, which may serve as a therapeutic target in HCC. SIGNIFICANCE: These findings describe the mechanism by which ZNF143 promotes HCC proliferation and provide important clues for exploring new targets and strategies for clinical treatment of human liver cancer.
Volume 80(12)
Pages 2599-2611
Published 2020-6-15
DOI 10.1158/0008-5472.CAN-19-3226
PII 0008-5472.CAN-19-3226
PMID 32312832
MeSH Animals Carcinoma, Hepatocellular / genetics* Carcinoma, Hepatocellular / mortality Carcinoma, Hepatocellular / pathology Carcinoma, Hepatocellular / surgery Cell Cycle Proteins / genetics* Cell Line, Tumor Cohort Studies DNA Methylation Datasets as Topic Dioxygenases / genetics* Dioxygenases / metabolism Gene Expression Regulation, Neoplastic* HEK293 Cells Hepatectomy Histone Demethylases / genetics* Histone Demethylases / metabolism Histones / genetics Humans Liver / pathology Liver / surgery Liver Neoplasms / genetics* Liver Neoplasms / mortality Liver Neoplasms / pathology Liver Neoplasms / surgery Male Mice Nuclear Proteins / genetics* Nuclear Proteins / metabolism Prognosis Promoter Regions, Genetic / genetics Tissue Array Analysis Trans-Activators / metabolism* Transcriptional Activation Xenograft Model Antitumor Assays
IF 9.727
Human and Animal Cells HuH-7