Abstract
Purpose The competing endogenous RNA (ceRNA) network regulatory has been investigated in the occurrence and development of many diseases. This research aimed at identifying the key RNAs of ceRNA network in pterygium and exploring the underlying molecular mechanism. Methods Differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs were obtained from the Gene Expression Omnibus (GEO) database and analyzed with the R programming language. LncRNA and miRNA expressions were extracted and pooled by the GEO database and compared with those in published literature. The lncRNA-miRNA-mRNA network was constructed of selected lncRNAs, miRNAs, and mRNAs. Metascape was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on mRNAs of the ceRNA network and to perform Protein-Protein Interaction (PPI) Network analysis on the String website to find candidate hub genes. The Comparative Toxicogenomic Database (CTD) was used to find hub genes closely related to pterygium. The differential expressions of hub genes were verified using the reverse transcription-real-time fluorescent quantitative PCR (RT-qPCR). Result There were 8 lncRNAs, 12 miRNAs, and 94 mRNAs filtered to construct the primary ceRNA network. A key lncRNA LIN00472 ranking the top 1 node degree was selected to reconstruct the LIN00472 network. The GO and KEGG pathway enrichment showed the mRNAs in ceRNA networks mainly involved in homophilic cell adhesion via plasma membrane adhesion molecules, developmental growth, regulation of neuron projection development, cell maturation, synapse assembly, central nervous system neuron differentiation, and PID FOXM1 PATHWAY. According to the Protein-Protein Interaction Network (PPI) analysis on mRNAs in LINC00472 network, 10 candidate hub genes were identified according to node degree ranking. Using the CTD database, we identified 8 hub genes closely related to pterygium; RT-qPCR verified 6 of them were highly expressed in pterygium. Conclusion Our research found LINC00472 might regulate 8 hub miRNAs (miR-29b-3p, miR-183-5p, miR-138-5p, miR-211-5p, miR-221-3p, miR-218-5p, miR-642a-5p, miR-5000-3p) and 6 hub genes (CDH2, MYC, CCNB1, RELN, ERBB4, RB1) in the ceRNA network through mainly PID FOXM1 PATHWAY and play an important role in the development of pterygium.
Highlights
Pterygium is a common ocular surface disease characterized by a triangular-shaped growth consisting of fibrotic subconjunctival connective tissue and hypertrophy of the overlying conjunctival epithelium [1]
Using the Comparative Toxicogenomic Database (CTD) database, we identified 8 hub genes closely related to pterygium; real-time fluorescent quantitative PCR (RT-qPCR) verified 6 of them were highly expressed in pterygium
Our research found LINC00472 might regulate 8 hub miRNAs and 6 hub genes (CDH2, MYC, CCNB1, RELN, ERBB4, RB1) in the competing endogenous RNA (ceRNA) network through mainly PID FOXM1 PATHWAY and play an important role in the development of pterygium
Summary
Pterygium is a common ocular surface disease characterized by a triangular-shaped growth consisting of fibrotic subconjunctival connective tissue and hypertrophy of the overlying conjunctival epithelium [1]. The development of pterygium is a complicated process involving cell proliferation, migration, inflammatory infiltrates, fibrosis, angiogenesis, and extracellular matrix breakdown [2]. Studies have demonstrated that noncoding RNAs served crucial roles in numerous diseases [6,7,8]. They are classified into two classes: small noncoding RNAs (microRNAs (miRNAs), small interfering RNAs, and transfer RNAs) and long noncoding RNAs (lncRNAs). The ceRNA network has been demonstrated in numerous diseases, in cancer. Zhu et al reported that 4 lncRNAs might act as potential therapeutic targets or candidate prognostic biomarkers in clear cell kidney carcinoma by reconstruction and comprehensive analysis of the ceRNA regulatory network [12]
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