Immunohistochemistry analyses of EGFRvIII, enhancer of zeste homolog 2 (EZH2) and aplysia ras homolog I (ARHI) were performed in tumor tissues from patients with glioma.
The expression of miR-32 and enhancer of zeste homolog 2 was detected by quantitative real-time polymerase chain reaction and Western blot in glioma tissues and cells.
Characterisation of EZH2 targets in de novo transformed cells, combined with analysis of glioma patient datasets and cell lines, reveals that acquisition of tumorigenic potential is accompanied by a transcriptional switch involving de-repression of spinal cord-specifying HOX genes and concomitant silencing of the empty spiracles homologue EMX2, a critical regulator of neurogenesis in the forebrain.
SIGNIFICANCE: EZH2 is involved in the generation of <i>IDH</i>-wild-type diffuse astrocytic gliomas and is a potential therapeutic target for this type of glioma.
We suggest that the expression of EZH2 is not associated with the PRC2 pathway and increases in patients with H3K27M-mutant diffuse midline glioma and a poor prognosis.
Among the epigenetic players, the H3K27 methyltransferase (MT) EZH2 (enhancer of zeste homologue 2) has been found overexpressed or mutated in several human cancers including gliomas, and its overexpression is associated with poor outcome in GBM.
The mechanistic assays disclosed that SNHG3 facilitated the malignant progression of glioma through epigenetically repressing KLF2 and p21 via recruiting enhancer of zeste homolog 2 to the promoter of KLF2 and p21.
Both cell clonal formation and xenograft assays showed that the downregulation of EZH2 inhibited glioma cell proliferation (P<0.05) and weakened tumorigenesis potency (P<0.05).
To uncover the role of EZH2 and its opponent ASHL2, a polycomb and trithorax group protein, respectively, on the radioresponsiveness of glioma cell lines.
Taken together, these data indicate that miRNA-driven EZH2 repression may provide evidence of the molecular mechanism for gliomagenesis and the novel therapeutic targets for glioma.
Moreover, correlation between the expressions of EZH2 and NOTCH intracellular domain 1 (NICD1) was observed in the clinical tumor samples, evidently supporting the existence of EZH2-NOTCH1 interaction in the gliomas and GSCs.
These data inferred that long non-coding RNA PVT1 could be served as an indicator of glioma prognosis, and PVT1-EZH2 regulatory pathway may be a novel therapeutic target for treating glioma.