Jichu yixue yu linchuang (Jun 2022)

Epigenetic regulation mechanism of EZH2 gene in hepatocellular carcinoma

  • ZHAO Yu-shan, JI Meng-die, DONG Yu-cheng, GUO Xin, SONG Bo-yuan, CHEN Yang

DOI
https://doi.org/10.16352/j.issn.1001-6325.2022.06.026
Journal volume & issue
Vol. 42, no. 6
pp. 864 – 870

Abstract

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Objective This study combined public data analysis with biological experiment using the tissues of hepato-cellular carcinoma to explore the epigenetic regulation mechanism of EZH2 gene which is potentially related to the progression of hepato-cellular carcinoma. Methods Using the TCGA's public clinical data of hepato-cellular carcinoma, the relation of EZH2 gene expression with tumor progression as well as prognosis was analyzed. Subsequently, the effect of EZH2 inhibitor GSK343(10 μmol/L) on the proliferation of hepato-cellular carcinoma cell line HepG2 was further analyzed by ATP cell activity assay and crystal violet assay. Then, the differentially expressed genes between EZH2 high expression group and low expression group in TCGA samples were analyzed. After that, the ChIP-seq public data of ENCODE was used to analyze the histone modification at the transcription starting site of EZH2 downstream target gene. Finally, RT-qPCR was used to detect the gene expression of downstream target genes regulated by EZH2. Results EZH2 gene-expression was significantly correlated with the progression of hepato-cellular carcinoma from stage 1 to stage 3(P＜0.05). Survival analysis showed that the high expression of EZH2 gene was significantly correlated with the poor prognosis of hepatocellular carcinoma(P＜0.05). The EZH2 inhibitor could significantly inhibit the proliferation of hepatocellular carcinoma cell line HepG2 in vitro (P＜0.05). Histone modification H3K27me3 was enriched at the transcription start site of EZH2 binding gene. There was 163 genes significantly different in EZH2 high expression group and low expression group and had EZH2 binding sites at their transcription start sites. The experiment verified that ADRA1A was a downstream target gene of EZH2. Conclusions EZH2 gene may affect expression of its downstream target genes through epigenetic regulation in hepato-cellular carcinoma.

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