From: EZH2 in hepatocellular carcinoma: progression, immunity, and potential targeting therapies
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] |