Ultraviolet-B (UVB) is a recognized risk factor for age-related cataract (ARC) and can cause various changes, including ubiquitination, in lens epithelial cells (LECs). However, the relationship between ubiquitination and ARC is unclear. Herein, we used UVB-irradiated human lens epithelial cell line (SRA01/04) representing the cell model of ARC to investigate the profile changes in the proteome and ubiquitome. A total of 552 differentially expressed proteins (DEPs) and 871 differentially ubiquitinated proteins (DUPs) were identified, and 9 ubiquitination motifs were found. Bioinformatics analysis revealed diverse pathways and biological processes of differential proteins and several DNA damage repair proteins that were potentially mediated via ubiquitin-proteasome pathway. We validated the decreased protein expression of DNA-directed RNA polymerase II subunit RPB2 (POLR2B) in both human cataract capsule tissues and UVB-treated SRA01/04 cells and found that treatment with proteasome inhibitor (MG-132) could reverse the protein level of POLR2B in UVB-irradiated SRA01/04 cells. Our data provide novel information regarding protein expressions and ubiquitination modifications in UVB-induced oxidative damage model. This study might offer a cell-level reference to further investigate the pathogenesis of ARC.

The pathology of age‐related cataract (ARC) mainly involves the misfolding and aggregation of proteins, especially oxidative damage repair proteins, in the lens, induced by ultraviolet‐B (UVB). MSH3, as a key member of the mismatch repair family, primarily maintains genome stability. However, the function of MSH3 and the mechanism by which cells maintain MSH3 proteostasis during cataractogenesis remains unknown. In the present study, the protein expression levels of MSH3 were found to be attenuated in ARC specimens and SRA01/04 cells under UVB exposure. The ectopic expression of MSH3 notably impeded UVB‐induced apoptosis, whereas the knockdown of MSH3 promoted apoptosis. Protein half‐life assay revealed that UVB irradiation accelerated the decline of MSH3 by ubiquitination and degradation. Subsequently, we found that E3 ubiquitin ligase synoviolin (SYVN1) interacted with MSH3 and promoted its ubiquitination and degradation. Of note, the expression and function of SYVN1 were contrary to those of MSH3 and SYVN1 regulated MSH3 protein degradation via the ubiquitin‐proteasome pathway and the autophagy‐lysosome pathway. Based on these findings, we propose a mechanism for ARC pathogenesis that involves SYVN1‐mediated degradation of MSH3 via the ubiquitin‐proteasome pathway and the autophagy‐lysosome pathway, and suggest that interventions targeting SYVN1 might be a potential therapeutic strategy for ARC.

To investigate the regulatory mechanism of pterygium formation, we detected differentially expressed messenger RNAs (DE-mRNAs) and differentially expressed circular RNAs (DE-circRNAs) in pterygium-associated conjunctival epithelium (PCE) and normal conjunctival epithelium (NCE). Genome-wide mRNA and circRNA expression profiles of PCE and NCE were determined using high-throughput sequencing. Bioinformatics analyses, including Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, gene set enrichment analysis (GSEA), and protein–protein interaction (PPI) analysis, were conducted. The microRNAs (miRNAs) interacting with the hub DE-mRNAs and DE-circRNAs were predicted and verified using real-time quantitative PCR (RT-qPCR). The data showed that there were 536 DE-mRNAs (280 upregulated and 256 downregulated mRNAs) and 78 DE-circRNAs (20 upregulated and 58 downregulated circRNAs) in PCE. KEGG enrichment analysis indicated that the DE-mRNAs were mainly involved in the following biological processes: IL-17 signalling pathway, viral protein interaction with cytokine and cytokine receptor, cytokine–cytokine receptor interaction, ECM-receptor interaction, and focal adhesion. The GSEA results revealed that the epithelial mesenchymal transition (EMT) process was significantly enriched in upregulated mRNAs. The pterygium-associated circRNA–miRNA–mRNA network was established based on the top 10 DE-circRNAs, 4 validated miRNAs (upregulated miR-376a-5p and miR-208a-5p,downregulated miR-203a-3p and miR-200b-3p), and 31 DE-mRNAs. We found that miR-200b-3p, as a regulator of FN1, SDC2, and MEX3D, could be regulated by 5 upregulated circRNAs. In addition, we screened out EMT-related DE-mRNAs, including 6 upregulated DE-mRNAs and 6 downregulated DE-mRNAs. The EMT-related circRNA–miRNA–mRNA network was established with the top 10 circRNAs, 8 validated miRNAs (upregulated miR-17-5p, miR-181a-5p, and miR-106a-5p, downregulated miR-124-3p, miR-9-5p, miR-130b-5p, miR-1-3p, and miR-26b-5P), and 12 EMT-related DE-mRNAs. We found that hsa_circ_0002406 might upregulate FN1 and ADAM12 by sponging miR-26b-5p and miR-1-3p, respectively, thus promoting EMT in pterygium. Briefly, the study provides a novel viewpoint on the molecular pathological mechanisms in pterygium formation. CircRNA–miRNA–mRNA regulatory networks participate in the pathogenesis of pterygium and might become promising targets for pterygium prevention and treatment.