Table 1.

Summary of EZH2 function and mechanism in HCC

Partner/target	Mechanism	Effect on HCC	Ref
FBP1/PKLR	EZH2 inhibits PKLR expression to inactivate NK cells residing in the liver.	promotes the occurrence and development of liver tumors.	[65]
E2F1/DDX11	DDX11 enhances the stability of EZH2 to downregulate P21. E2F1 cooperates with EZH2 to upregulate DDX11 mRNA expression.	promotes HCC cell proliferation.	[45]
CHD5	EZH2 promotes trimethylation of H3K27 by directly binding to the promoter site of CHD5, resulting in downregulation of CHD5 expression.	promotes HCC cell proliferation and invasion.	[35]
SOX21-AS1	Recruit EZH2 to the promoter of P21 and inhibit expression of P21.	promotes HCC growth and metastasis	[55]
LINC00978	Recruits EZH2 to the promoter of p21, resulting in enrichment of H3K27me3 at the promoter and suppressing p21 and E-cadherin expression.	promotes HCC growth and metastasis.	[34]
SPRY4-IT1	Recruit EZH2 to the promoter of E-cadherin and inhibit the expression of E-cadherin through enrichment of H3K23me3 at the promoter of E-cadherin.	promotes HCC cell invasion and proliferation.	[44]
FOXA2	EZH2 represses expression of LINC00261 to promote FOXA2 transcription.	promotes HCC invasion and metastasis.	[47]
LINC01419	LINC01419 binds to EZH2, resulting in H3K27me3 enrichment at the promoter region and suppresses transcription of RECK.	promotes HCC growth and metastasis	[41]
LNC-β-CATM	LNC-β-CATM associates with EZH2 and β-catenin, leading to β-catenin methylation, thereby activating Wnt-β-catenin signaling.	correlates positively with HCC prognosis and severity.	[42]
HOTAIR	Recruits EZH2 to upregulate expression of DMMTs to inhibit the expression of miR-122 to activate cyclin G1.	promotes HCC growth.	[43]
miR-622	EZH2 inhibits miR-622 expression by promoting trimethylation of H3K27 at the miR-622 promoter region.	promotes hepatoma cell growth and migration.	[29]
circRNA-LRIG3	CircRNA-LRIG3 binds to EZH2 and STAT3 to promote EZH2-induced STAT3 activation.	promotes HCC growth and metastasis.	[50]
Galectin-9	EZH2 promotes expression of Galectin-9 by inhibiting the transcription of miR-22.	promotes CD4+T-cell senescence.	[59]
NF-κB	EZH2 forms a complex with NF-κB (P50 and P65) under induction of CCRK to promote transcription of IL-6.	promotes immune evasion and MDSC expansion.	[52]
ULBP1	EZH2 increases ULBP1 promoter DNA methylation through DNMT3 and downregulates NKG2D ligand expression in hepatoma cells.	inhibits NK-cell-mediated cytotoxicity.	[63]
CXCL10	EZH2 suppresses transcription of CXCL10 by upregulating the level of H3K27me3 on its promoter.	attenuates NK-cell recruitment at tumor sites.	[62]