Thus, we conclude that epigenetic silencing of miR-218 via EZH2-mediated H3K27 trimethylation is involved in the acquisition of CSC-like properties and malignant transformation of HBE cells induced by CSE and thereby contributes to the carcinogenesis of cigarette smoke.
Enhancer of zeste homolog 2 (EZH2) plays a key role in tumorigenesis and cancer progression through epigenetic gene silencing and chromatin remodeling.
In this review, we highlight the critical role of EZH2 as a master regulator of tumorigenesis in the prostate, bladder and the kidney through epigenetic control of transcription as well as a modulation of various critical signaling pathways.
We therefore analyzed the expression of the PcG genes (EZH2, BMI-1, EED, SUZ12) in relation to that of the nephric-progenitor genes (WT1, PAX2, SALL1, SIX2, CITED1) using real-time polymerase chain reaction and methylation assays during renal development, regeneration, and tumorigenesis.
EZH2 overexpression increased H3K27me3 levels and thereby silenced the expression of Wnt signal inhibitors, resulting in activation of Wnt/β-catenin signaling and subsequently induction of cell proliferation and tumorigenesis.
Somatic defects in additional genes, including β-catenin, POT1 and EZH2 may contribute to parathyroid adenoma formation but, for most, their ability to drive parathyroid tumorigenesis remains to be demonstrated experimentally.
In conclusion, GNAI1, NCAPH, MMP9, AURKA and EZH2 should be examined in further studies for the possibility of their participation in the carcinogenesis and carboplatin response of SOC.
Interestingly, only a minority of cases of blastic plasmacytoid dendritic cell neoplasm exhibited high EZH2 expression, and only a minority of these cases showed p-ERK1/2 co-expression, suggesting that alternative mechanisms may contribute to tumorigenesis in this aggressive neoplasm.
Therefore, this review provides a comprehensive overview on the oncogenic role of EZH2 during tumorigenesis and highlights the multifaceted role of EZH2, as either a transcriptional activator or repressor depending on the cellular context.
It has been reported that the trimethylation of histone 3 on lysine 27 (H3K27me3) is required for enhancer of zeste homology 2 (EZH2)-mediated repression of various genes essential for tumorigenesis and tumor development.