Genome-Wide Identification of Circular RNAs as a Novel Class of Putative Biomarkers for an Ocular Surface Disease

Cell Physiol Biochem. 2018;47(4):1630-1642. doi: 10.1159/000490982. Epub 2018 Jun 27.

Abstract

Background/aims: Pterygium is a common ocular surface disease with an unknown etiology and threatens vision as it invades into the cornea. Circular RNAs (circRNAs) are a novel class of RNA transcripts that participate in several physiological and pathological processes. However, the role of circRNAs in pathogenesis of pterygium remains largely unknown.

Methods: Genome-wide circRNA expression profiling was performed to identify pterygium -related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was performed to predict the function of differentially expressed circRNAs in pterygium. MTT assays, Ki67 staining, Transwell assay, Hoechst 33342 staining, and Calcein-AM/PI staining were performed to determine the effect of circRNA silencing on pterygium fibroblast and epithelial cell function.

Results: Approximately 669 circRNAs were identified to be abnormally expressed in pterygium tissues. GO analysis demonstrated that the host genes of differentially expressed circRNAs were targeted to extracellular matrix organization (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis showed that dysregulated circRNAs-mediated regulatory networks were mostly enriched in focal adhesion signaling pathway. Notably, circ_0085020 (circ-LAPTM4B) was shown as a potential biomarker for pterygium. circ_0085020 (circ-LAPTM4B) silencing affected the viability, proliferation, migration, and apoptosis of pterygium fibroblast and epithelial cells in vitro.

Conclusions: This study provides evidence that circRNAs are involved in the pathogenesis of pterygium and might constitute promising targets for the therapeutic intervention of pterygium.

Keywords: Circular RNA; Pterygium; Pterygium epithelium; Pterygium fibroblast.

MeSH terms

  • Biomarkers / metabolism
  • Epithelial Cells* / metabolism
  • Epithelial Cells* / pathology
  • Fibroblasts* / metabolism
  • Fibroblasts* / pathology
  • Genome-Wide Association Study*
  • Humans
  • Pterygium* / genetics
  • Pterygium* / metabolism
  • Pterygium* / pathology
  • RNA* / biosynthesis
  • RNA* / genetics

Substances

  • Biomarkers
  • RNA