Comprehensive Analysis of Differentially Expressed Circular RNAs in Keloid Dermal Tissues

Abstract

Background Keloid is a dermal fibroproliferative disease with various etiologies and unclear pathogenesis. Recent studies have revealed that circular RNAs (circRNAs) exerted regulatory functions through a competing endogenous RNA (ceRNA) pathway in keloid progression. However, the expression profiles of circRNAs in keloid dermal tissues (KDTs) remain unknown. This study aimed to identify differentially expressed circRNAs (DECs) and genes (DEGs) in KDTs, as well as to investigate the potential biological functionsof circRNAs based on the circRNA-miRNA-mRNA ceRNA network. Results Through high-throughput RNA sequencing (RNA-seq), we revealed 3467 DEGs (865 up- and 2602 down-regulated) and 330 DECs (162 up- and 168 down-regulated) in KDTs. To reveal the functions of DECs preliminarily, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for the host genes. Further, the up- and down-regulated DECs-miRNAs-DEGs regulatory networks were constructed, respectively. The functional prediction for the target genes showed that the up-regulated ceRNA network was associated with extracellular matrix and multiple cellular functions. The down-regulated ceRNA network was enriched in cell-cell junction and other biological processes. Cytoscape was used to visualize each network's protein-protein interaction (PPI) network and identify hub genes. By quantitative Real-Time PCR (qRT-PCR), hsa_circ_0060927, hsa_circ_0071410, hsa_circ_0058092, hsa_circ_0002874, hsa_circ_0004682, hsa_circ_0072688, hsa_circ_0006401, and hsa_circ_0055954 were identified significantly up-regulated in KDTs. Within, hsa_circ_0072688, which was up-regulated both in KDTs and keloid dermal fibroblasts (KDFs), and located in the cytoplasm, might be a key circRNA and affect the progression of keloid by impacting extracellular matrix, cell adhesion, and cell apoptosis, etc. Conclusion This study not only filled a gap in the circRNA library of KDTs but also laid a foundation for probing the biological function of DECs in keloids. Hsa_circ_0072688 was thought to be a key circRNA and more experimental support is needed.