Profiling and Integrated Analysis of the ERCC6-regulated circRNA-miRNA-mRNA Network in Lens Epithelial Cells

ABSTRACT

Purpose: To explore the regulatory role of ERCC6 in the circRNA-miRNA-mRNA network using a cellular ERCC6 overexpression model (OE-ERCC6) in lens epithelial cells.

Methods: The expression profiles of circRNAs, miRNAs and mRNAs were determined by RNA-seq, and a regulatory circRNA-miRNA-mRNA network was constructed via bioinformatics. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used for the functional annotation of circRNA host genes, differentially expressed (DE) genes, and miRNA targets.

Results: The DE molecules between the OE-ERCC6 and control groups included 269 circRNAs, 241 miRNAs and 3500 mRNAs. We validated 5 selected DE reads of circRNAs (hsa_circ_0001009, hsa_circ_0002024, hsa_circ_0004592, hsa_circ_0001900 and hsa_circ_0001017). Subsequent bioinformatics analysis revealed that the DE circRNAs are mainly involved in oxidative stress- and cell death-related signaling pathways. Finally, a circRNA-miRNA-mRNA network focusing on DNA damage and cell death, which involved 5 circRNAs, 13 miRNAs and 107 mRNAs, was constructed.

Conclusion: We constructed a circRNA-miRNA-mRNA network that is regulated by ERCC6. DE circRNAs have the potential to become therapeutic targets related to the lens lesions observed in ARC. The establishment of related in vivo and in vitro models could be a future direction to confirm these hypotheses.

KEYWORDS:

• ERCC6
• circular RNA
• lens epithelial cells

Disclosure Statement

The authors declare no conflict of interest.

Supplementary material

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Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81770906, 81500706 and 81974129), the Postdoctoral Science Foundation of China (2020M671562), the Postdoctoral Science Foundation of Jiangsu Province (2020Z318), the Science and Technology Project of Nantong Municipality (MS22019012, JCZ19088 and MS12019030), and the Project of Nantong Municipal Health Commission (QA2019061)