Diagnostic Markers and Molecular Dysregulation Mechanisms in the Retinal Pigmented Epithelium and Retina of Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a chronic and progressive macular degeneration disease, which can also lead to serious visual loss. In our research, we aim to efficiently identify biomarkers relevant for AMD diagnosis. We collected the gene expression data of retinal segmented epithelium (RPE) and retina tissues of GSE29801 and GSE135092 and performed differential expression analysis. The differentially expressed genes (DEGs) related to the RPE and retina in the two sets of data were identified and enriched by intersection analysis. A PPI network was constructed for intersection genes, and the top 20 genes with the largest connectivity in the network were selected as candidate genes. The LASSO model was used to identify key genes from candidate genes, and the nomogram and ROC curve were used to evaluate the diagnostic ability of key genes. We identified 464 intersection genes associated with RPE and 509 intersection genes associated with retina. The TGF-beta signaling pathway was enriched by RPE-related DEGs, while oxidative phosphorylation was enriched by retina-related DEGs. Among the candidate genes of RPE, the LASSO model identified 7 key genes. MAPK1 and LUM can predict the clinical diagnosis of AMD. Among the candidate genes of retina, the LASSO model identified four key genes. PTPN11 has the highest predictive diagnostic value. The results suggest that the imbalance mechanism of RPE in AMD may be related to the TGF-beta signaling pathway, and the imbalance mechanism of the retina may be related to oxidative phosphorylation. MAPK1 and LUM are potential diagnostic markers of RPE, and PTPN11 is a potential diagnostic marker of the retina. Also, our results provide a theoretical basis for better understanding the molecular mechanisms of AMD onset and treatment in the future.

The Tumorigenic Properties of EZH2 are Mediated by MiR-26a in Uveal Melanoma.

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.