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Background: Recently, it has been reported that miRNA is involved in pterygium, however the exact underlying mechanism in pterygium is unrevealed and require further investigation., Methods: The differential expression of miRNA in pterygium was profiled using microarray and validated with quantitative real-time polymerase chain reaction (qRT-PCR). Human conjunctival epithelial cells (HCEs) were cultured and treated with transforming growth factor β (TGF-β) and epidermal growth factor (EGF) and transfected with miR-199a-3p/5p mimic and inhibitor. Markers of epithelial-mesenchymal transition (EMT) in HCEs were detected using western blot and immunohistochemistry. Cell migration ability was determined using wound healing and transwell assay, while apoptosis was determined by flow cytometry. The target genes of miR-199a were confirmed by the dual-luciferase reporter assay., Results: TGF-β and EGF could induced EMT in HCEs and increase miR-199a-3p/5p but suppress target genes, DUSP5 and MAP3K11. With the occurrence of EMT, cell migration ability was enhanced, and apoptosis was impeded. Promoting miR-199a-3p/5p expression could induce EMT in HCEs without TGF-β and EGF, while suppressing miR-199a-3p/5p could inhibit EMT in TGF-β and EGF induced HCEs. In a word, TGF-β and EGF induced EMT could be regulated with miR-199a-3p/5p-DUSP5/MAP3K11 axes. The validated results in tissues showed that, compared with control conjunctival tissues, miR-199a-3p/5p were more overexpressed in pterygium, while DUSP5/MAP3K11 were lower expressed. In addition, bioinformatics analysis indicated the miR-199a-3p/5p-DUSP5/MAP3K11 was belong to MAPK signalling pathway., Conclusions: TGF-β and EGF induce EMT of HCEs through miR-199a-3p/5p-DUSP5/MAP3K11 axes, which explains the pathogenesis of EMT in pterygium and may provide new targets for pterygium prevention and therapy.

Purpose: Signal transducer and activator of transcription 3 (STAT3) is a DNA-binding protein that regulates various biologic processes, including cell growth, apoptosis, and malignant transformation. Abnormal activation of STAT3 is associated with many diseases, and there is currently no relevant study on the pathogenesis of pterygium. The purpose of this study was to investigate the expression and clinical significance of STAT3, HIF-1α, and VEGF in pterygium at different stages., Methods: Immunohistochemistry was used to study the expression levels of STAT3, HIF-1α, and VEGF in 50 cases of pterygium and 20 cases of control conjunctival tissue. The expression intensity of the three proteins was evaluated with Image-Pro Plus 6.0 image analysis software., Results: In the pterygium group, the positive rates for STAT3, HIF-1α, and VEGF were 82.0%, 86.0%, and 84.0%, respectively, while those in the normal conjunctiva group were 40.0%, 25.0%, and 15.0%. The expression of STAT3, HIF-1α, and VEGF in pterygium was higher than that in control conjunctiva, and the expression in advanced pterygium was statistically significantly higher than that in stationary pterygium (p < 0.01). The expression levels of STAT3 and HIF-1α in pterygium were related to the length and depth of the corneal invasion of pterygium. The expression level of VEGF in pterygium was related to the length of pterygium, but not to the depth. In addition, there was a significant positive correlation between the expression of STAT3, HIF-1α, and VEGF (p < 0.01)., Conclusions: For the first time, the expression levels of the STAT3, HIF-1α, and VEGF proteins were detected simultaneously in pterygium tissue. Compared with normal conjunctiva, STAT3, HIF-1α, and VEGF were highly expressed in pterygium, and the expression in advanced pterygium tissue was more significant than in the stationary pterygium tissue. It is suggested that STAT3 may directly or through HIF-1α promote VEGF expression and participate in the growth and angiogenesis of pterygium. Targeting STAT3 may provide a new direction for the treatment of pterygium., (Copyright © 2020 Molecular Vision.)

Purpose: MiRNAs have been widely analyzed in the occurrence and development of many diseases, including pterygium. This study aimed to identify the key genes and miRNAs in pterygium and to explore the underlying molecular mechanisms., Methods: MiRNA expression was initially extracted and pooled by published literature. Microarray data about differentially expressed genes was downloaded from Gene Expression Omnibus (GEO) database and analyzed with the R programming language. Functional and pathway enrichment analyses were performed using the database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction network was constructed with the STRING database. The associations between chemicals, differentially expressed miRNAs, and differentially expressed genes were predicted using the online resource. All the networks were constructed using Cytoscape., Results: We found that 35 miRNAs and 301 genes were significantly differentially expressed. Functional enrichment analysis showed that upregulated genes were significantly enriched in extracellular matrix (ECM) organization, while downregulated genes were mainly involved in cell death and apoptotic process. Finally, we concluded the chemical-gene affected network, miRNA-mRNA interacted networks, and significant pathway network., Conclusion: We identified lists of differentially expressed miRNAs and genes and their possible interaction in pterygium. The networks indicated that ECM breakdown and EMT might be two major pathophysiological mechanisms and showed the potential significance of PI3K-Akt signalling pathway. MiR-29b-3p and collagen family (COL4A1 and COL3A1) might be new treatment target in pterygium.