Gene Profiling of Circular RNAs in Keloid-prone Individuals and ceRNA Network Construction During Wound Healing

Epigenetic alterations of non-coding RNA (ncRNA) are pivotal in the continuous activation and differentiation of fibroblasts in keloid. However, the epigenetic mechanism of circRNA in keloid is still not clear yet. In this study, we aimed to investigate the interplay among differentially expressed circRNAs, miRNAs, and mRNAs during wound healing in keloid-prone individuals, construct a competing endogenous RNA (ceRNA) network, and gain an in-depth insight into the pathophysiological mechanisms underlying keloid development. Utilizing bioinformatic methods, we analyzed the expression profiles from the GSE113621 database. We identified 29 differentially expressed circRNAs (DEcircRNAs) in keloid-prone individuals during wound healing, from which we constructed 14 ceRNA networks. Subsequently, we validated the expression of predicted DEcircRNAs in keloid tissues and elucidated the ceRNA network involving circ_064002 and fibronectin-1 (FN1) through competing miR-30a/b-5p. Knocking down circ_064002 led to down-regulation of FN1 expression and various cellular functions in keloid-derived fibroblasts (KFs), including cell viability, migration, invasion, and repair capacity. Our study introduces a novel approach to explore the presence of DEcircRNAs and the ceRNA regulatory network during wound healing in keloid-prone individuals through in-depth mining of GEO data and also proves the epigenetic regulatory mechanism of circ_064002 in KFs. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .