Table 1 Summary of EZH2 function and mechanism in HCC

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]