Fig. 2

Various mechanisms by which EZH2 regulates the proliferation and metastasis of HCC cells. (i) EZH2 exerts its oncogenic effects on liver cancer through a complex interplay of molecular mechanisms. EZH2 impedes the expression of LINC00261, miR-122, LINC00978, SOX21-AS1, CHD5, and RECK via mediation of H3K27 trimethylation within their respective promoter regions, thus leading to enhanced proliferation and invasion of liver cancer cells. (ii) EZH2 also enhances CXCR4 expression by suppressing miR-622 expression to up-regulate CXCR4/CXCL12, RAF/MEK/ERK, and PI3K/ATK pathways, promoting the proliferation and metastasis of HCC cells. EZH2 is selectively recruited by LINC01419, LINC00978, and SPRY4-IT1 to the promoters of its target genes RECK and β-cadherin, causing down-regulation of β-cadherin and up-regulation of MMPs via mediating trimethylation (iii) EZH2 facilitates the methylation of STAT3 via formation of a complex with circRNA-LRIG3 and STAT3, resulting in the phosphorylation and activation of STAT3. IL-6 can activate STAT3 via the JAK/STAT3 pathway, thereby inducing the expression of Twist. In these ways, EZH2 promotes the metastasis and invasion of liver cancer cells