Not only two enzymes with the same function (KDM6A and KDM6B), but also those with opposite functions (EZH2 versus KDM6A or KDM6B) synergistically affect H3K27me consequences such as gastric cancer susceptibility.
The binding of ALKBH5 and NEAT1 influences the expression of EZH2 (a subunit of the polycomb repressive complex) and thus affects GC invasion and metastasis.
However, the clinical significance and molecular mechanisms of EZH2 controlling gastric cancer cell proliferation and invasion are not well documented.
Our findings show that SNHG6 knockdown inhibits GC development by upregulating p21; this effect is dependent on the activation of the JNK pathway and suppression of EZH2 expression.
Besides, Ezh2 led to the acquisition of epithelial-mesenchymal transition (EMT) phenotype of GC cells and enhanced GC cell migration and invasion capacity.
This interaction resulted in sequestration of miR-26 from its target EZH2, which released the suppression on EZH2, and thereby led to EZH2 overexpression in gastric cancer.
Taken together, these findings show that SP1-activated LINC00673 exerts an oncogenic function that promotes GC development and progression, at least in part, by functioning as a scaffold for LSD1 and EZH2 and repressing KLF2 and LATS2 expression.
STAT3 signaling was correlated with EZH2 expression in GC (R = 0.373, P = 0.003), which was consistent with our data showing that STAT3 as the transcriptional factor enhanced EZH2 transcriptional activity by binding the relative promoter region (-214 ~ -206).
Collectively, these results indicated that EZH2 and DNMT1-mediated epigenetic silencing contributed to the progression of gastric cancer and glioblastoma, and therefore represents a novel therapeutic target for malignant tumors.
We found five single nucleotide polymorphisms (SNP; rs12670401, rs6464926, rs2072407, rs734005, and rs734004) of EZH2 gene were significantly associated with the risk of gastric cancer.
CXXC4 is a novel potential tumor suppressor directly regulated by EZH2, and its expression is a significant prognosis factor for patients with early stages of gastric cancer.