构建 lncRNA-miRNA-mRNA 调控网络探究翼状胬肉的分子机制。

PURPOSE: This research explores the aberrant expression of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) in pterygium. A competitive endogenous RNA (ceRNA) network was constructed to elucidate the molecular mechanisms in pterygium. METHODS: We obtained the differentially expressed mRNAs based on three datasets (GSE2513, GSE51995, and GSE83627), and summarized the differentially expressed miRNAs (DEmiRs) and differentially expressed lncRNAs (DELs) data by published literature. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI), and gene set enrichment analysis (GSEA) analysis were performed. DEmiRs were verified in GSE21346, and the regulatory network of hub mRNAs, DELs, and DEmiRs were constructed. RESULTS: Overall, 40 upregulated and 40 downregulated differentially expressed genes (DEGs) were obtained. The KEGG enrichment showed the DEGs mainly involved in extracellular matrix (ECM)-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway. The GSEA results showed that cornification, keratinization, and cornified envelope were significantly enriched. The validation outcome confirmed six upregulated DEmiRs (miR-766-3p, miR-184, miR-143-3p, miR-138-5p, miR-518b, and miR-1236-3p) and two downregulated DEmiRs (miR-200b-3p and miR-200a-3p). Then, a ceRNA regulatory network was constructed with 22 upregulated and 15 downregulated DEmiRs, 4 downregulated DELs, and 26 upregulated and 33 downregulated DEGs. The network showed that lncRNA SNHG1/miR-766-3p/FOS and some miRNA-mRNA axes were dysregulated in pterygium. CONCLUSIONS: Our study provides a novel perspective on the regulatory mechanism of pterygium, and lncRNA SNHG1/miR-766-3p/FOS may contribute to pterygium development.

目的：本研究探讨了翼状胬肉中长链非编码 RNA（lncRNA）、微小 RNA（miRNA）和信使 RNA（mRNA）的异常表达。构建了竞争性内源性 RNA（ceRNA）网络，以阐明翼状胬肉中的分子机制。

方法：我们根据三个数据集（GSE2513、GSE51995 和 GSE83627）获得差异表达的 mRNAs，并通过已发表的文献总结差异表达的 miRNAs（DEmiRs）和差异表达的 lncRNAs（DELs）数据。进行了基因本体论（GO）、京都基因与基因组百科全书（KEGG）通路、蛋白质-蛋白质相互作用（PPI）和基因集富集分析（GSEA）分析。在 GSE21346 中验证了 DEmiRs，并构建了枢纽 mRNAs、DELs 和 DEmiRs 的调控网络。

结果：总体而言，获得了 40 个上调和 40 个下调的差异表达基因（DEGs）。KEGG 富集显示，DEGs 主要参与细胞外基质（ECM）-受体相互作用、焦点黏附以及 PI3K-Akt 信号通路。GSEA 结果表明，角质化、角化和角质化包膜显著富集。验证结果证实了六个上调的 DEmiRs（miR-766-3p、miR-184、miR-143-3p、miR-138-5p、miR-518b 和 miR-1236-3p）和两个下调的 DEmiRs（miR-200b-3p 和 miR-200a-3p）。然后，构建了一个 ceRNA 调控网络，其中包含 22 个上调和 15 个下调的 DEmiRs、4 个下调的 DELs 和 26 个上调和 33 个下调的 DEGs。该网络表明，lncRNA SNHG1/miR-766-3p/FOS 及一些 miRNA-mRNA 轴在翼状胬肉中失调。

结论：本研究为翼状胬肉的调控机制提供了新的视角，lncRNA SNHG1/miR-766-3p/FOS 可能参与翼状胬肉的发生发展。