Background: Keloid is an excessive fibrosis disease caused by the abnormal proliferation of collagen fibers following trauma. Previous studies have shown that genetic factors have been considered to play important roles in keloid formation. This study is aimed to investigate the regulatory network of messenger RNAs (mRNAs) microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in keloid, and identifying its key biomarkers.
Methods: We performed RNA-seq and miRNA-seq on keloid and normal skin samples. Sequencing datasets were analyzed by bioinformatics. Gene ontology (GO) and pathway analysis presented the characteristics of associated protein-coding genes. Differentially expressed ceRNAs were validated by quantitative reverse transcriptase-PCR (qRT-PCR).
Results: We identified a total of 319 lncRNAs, 1,533 mRNAs and 40 miRNAs as keloid-specific RNAs. Both the GO biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed for 1,219 specific genes with differentially expressed mRNAs. Then, with 509 key lncRNAs, 25 miRNAs, and 94 mRNAs, we constructed a ceRNA network and explored any potential underlying mechanisms. In the regulation of the actin cytokeleton pathway, we validated 2 pairs of ceRNAs EGFR/miR-370-3p/lnc-GLB1L-1 and ITGB5/ miR-204/ lnc-CASP9-3 in another sample size in keloid.
Conclusions: Through RNA-seq and miRNA-seq, we identified keloid-associated lncRNAs, mRNAs and miRNAs, which can be used as potential therapeutic targets and biomarkers for keloid. Our study may lay a foundation for future pathogenesis studies.
Keywords: Keloid; RNA sequence; competing endogenous RNA; long non-coding RNA (lncRNA).
2020 Annals of Translational Medicine. All rights reserved.