Abstract
Background: The polycomb group protein enhancer of zeste homolog 2 (EZH2) has been found to be highly expressed in various tumors, and microRNA-26a (miR-26a) is often unmodulated in cancers. However, the functions of these two molecules in uveal melanoma (UM) and their relationships have not been reported. Methods: We explored the effects of the miR-26a–EZH2 axis in UM by examining the levels of miR-26a and EZH2. The EZH2 levels in various tumor types and the correlations between EZH2 levels and overall survival and disease-free survival were reanalyzed. The binding of miR-26a to the 3′-untranslated region of EZH2 mRNA was measured using the luciferase reporter assay. The regulation of EZH2 gene expression by miR-26a was also identified, and the effect of elevated EZH2 expression on UM cell function was further examined. Results: miR-26a was downregulated and EZH2 was upregulated in UM cells. Overexpression of miR-26a inhibited cell proliferation, and knockdown of EZH2 suppressed cell growth. EZH2 was a direct target of miR-26a in UM cells. The knockout of EZH2 mimicked the tumor inhibition of miR-26a in UM cells, whereas the reintroduction of EZH2 abolished this effect. In addition, a network of EZH2 and its interacting proteins (UBC, CDK1, HDAC1, SUZ12, EED) was found to participate in miR-26a-mediated tumor progression. Conclusion: The newly identified miR-26a–EZH2 axis may be a potential target for the development of treatment strategies for UM.
Highlights
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults (Rodríguez et al, 2016)
The results revealed that enhancer of zeste homolog 2 (EZH2) was upregulated in various tumor types (Figure 1A)
Further analysis showed that high EZH2 expression was significantly associated with overall survival and disease-free survival in patients with UM (Figure 1B)
Summary
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults (Rodríguez et al, 2016). Micro-ribonucleic acids (miRNAs) are a class of small, noncoding, 21 to 25-nucleotide-long RNA molecules (Tomar et al, 2020). They can cause degradation or inhibit translation of target genes by targeting the 3′-untranslated region (3′-UTR) of mRNA. A recent study found that the EZH2/MiR-26a Axis in UM abnormal expression of miRNAs is closely related to tumors, and that it exerts an effect on tumor suppressor genes and protooncogenes in vivo, regulating the occurrence, development, and outcome of tumors (Iorio and Croce, 2012). The functions of these two molecules in uveal melanoma (UM) and their relationships have not been reported
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