Abstract Objectives Hypertrophic scar (HS), a type of pathological scar, arises from excessive fibrosis in the process of skin wound repair. Circular RNAs (circRNAs) are involved in regulating fibroblast functions in HS, but the role of circ₀008667 remains unclear. To investigate the expression and regulatory mechanism of circ₀008667 in hypertrophic scar fibroblasts (HSFs). Methods This study employed HSFs and normal skin fibroblasts (NSFs). The expression levels of circ₀008667, miR-324-5p, HOXA9, and collagen-related genes were detected using RT-qPCR. After cell transfection, the impacts of the relevant factors on HSFs proliferation and apoptosis were examined using CCK-8 and apoptosis assay. The target binding relationship is determined using the dual-luciferase reporter assay. Results Circ₀008667 was highly expressed in HSFs. Its silencing inhibited HSF proliferation, promoted apoptosis, and reduced collagen-related genes, including Collagen Type I (Col I), Collagen Type III (Col III), and α-smooth muscle actin (α-SMA) expression. Circ₀008667 can directly interact with miR-324-5p and negatively regulate its expression. MiR-324-5p reverses the promoting effects of circ₀008667 on HSFs. HOXA9 is a target of miR-324-5p, and when overexpressed, it can reverse the inhibitory effects of miR-324-5p. Conclusions Circ₀008667 mediates excessive proliferation and fibrosis of HSFs via regulating the miR-324-5p/ HOXA9 axis, suggesting its potential as a target for HS treatment.
Miao et al. (2026) studied this question.