journal contribution
posted on 2023-03-31, 03:01 authored by Lili Zhang, Qi Huo, Chao Ge, Fangyu Zhao, Qingqing Zhou, Xiaoxia Chen, Hua Tian, Taoyang Chen, Haiyang Xie, Ying Cui, Ming Yao, Hong Li, Jinjun Li Supplementary Figures includes 8 supplementary figures and Legends. Supplementary Figure 1 shows the expression of ZNF143 in different cancers in HCCDB database. Supplementary Figure 2 mainly shows the relationship between ZNF143 and cell cycle transition in HCC cells. Supplementary Figure 3 shows the role of CDC6 in HCC cells. Supplementary Figure 4 mainly shows the enrichment of H3K4me3 or H3K27me3 in different promoter regions of CDC6 after overexpressing ZNF143. Supplementary Figure 5 shows the relationship between MDIG and cell cycle transition in HCC cells. Supplementary Figure 6 shows the role of CBX3, CBX5 on mediating the recruitment MDIG to CDC6 promoter. Supplementary Figure 7 shows MDIG is required for ZNF143 mediated HCC cell proliferation. Supplementary Figure 8 mainly shows the clinical significance of MDIG and CDC6 in HCC.
Funding
National Key Program for Basic Research of China
National Natural Science Foundation of China
National Key Sci-Tech Special Project of China
Shanghai Municipal Commission of Health and Family Planning Foundation
History
ARTICLE 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.
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.
