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The role of EZH2 as a potential therapeutic target in retinoblastoma

Enhancer of zeste homolog 2 (EZH2) has been reported selectively expressed in postnatal human retinoblastoma (RB). While, the contribution of EZH2 in progression of RB and its clinical importance has not been clarified. Here, immunohistochemistry (IHC) was performed on tumor specimens from 53 RB patients. UNC1999 and GSK503, inhibitors targeting EZH2, were incubated with human RB cell line WERI-Rb-1 and Y79 to assess the role and mechanism of EZH2 in RB proliferation, metastasis and tumor glycolysis. Administration of UNC1999 in subcutaneous tumor model of RB was conducted. The results showed that highly expressed EZH2 in RB tissues was significantly associated with the poor overall survival. UNC1999 and GSK503 inhibited proliferation, migration, invasion and tumor glycolysis of RB. Results in mouse xenograft model confirmed the inhibitory effect of UNC1999 on tumor growth of RB and the regulation effect of EZH2 to STAT3/FoxO1 signaling pathway. Therefore, EZH2 is rewarding to study as a potential target for anti-RB treatment.

 

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The study you mentioned investigated the expression and clinical significance of Enhancer of zeste homolog 2 (EZH2) in postnatal human retinoblastoma (RB). The researchers performed immunohistochemistry (IHC) on tumor samples from 53 RB patients and conducted in vitro and in vivo experiments to assess the role and mechanism of EZH2 in RB progression.

The results of the study demonstrated that EZH2 was highly expressed in RB tissues, and this elevated expression was significantly associated with poor overall survival in RB patients. To further explore the functional importance of EZH2, the researchers used two EZH2 inhibitors, UNC1999 and GSK503, and tested them on the human RB cell lines WERI-Rb-1 and Y79.

The findings revealed that treatment with UNC1999 and GSK503 inhibited RB cell proliferation, migration, invasion, and tumor glycolysis. Additionally, in a mouse xenograft model of RB, administration of UNC1999 resulted in the inhibition of tumor growth, confirming the therapeutic potential of targeting EZH2 for anti-RB treatment.

Furthermore, the study investigated the molecular mechanism underlying the effects of EZH2 inhibition. It was observed that EZH2 regulated the STAT3/FoxO1 signaling pathway, which is involved in cell growth, survival, and metastasis. The inhibition of EZH2 by UNC1999 affected this pathway, suggesting a potential mechanism by which EZH2 influences RB progression.

In summary, the study provides evidence that EZH2 plays a significant role in RB progression and highlights its clinical importance as a potential therapeutic target for anti-RB treatment. The findings suggest that targeting EZH2 using inhibitors like UNC1999 could be a promising strategy to inhibit RB cell growth, metastasis, and tumor glycolysis.