MiR-203 regulates keloid fibroblast proliferation, invasion, and extracellular matrix expression by targeting EGR1 and FGF2

Abstract

Keloid is a fibrous benign tumor of the skin caused by increased fibroblast proliferation and overproduction of extracellular matrix (ECM) in the dermis. Several miRNAs exhibit critical roles in regulating keloid development. This is study aimed to investigate the effects and mechanisms of miR-203 in keloid fibroblasts. The miR-203 expression was detected by qRT-PCR; The cell viability was measured by MTT assay; The cell proliferation was measured by BrdU assay; The cell invasion was measured by Transwell assay; The protein expression was detected by Western blot; The target relationship between miR-203 and mRNA was measured by dual-luciferase assay. We found that miR-203 was significantly downregulated in both keloid tissues and keloid fibroblasts from keloid patients. MiR-203 overexpression in vitro led to a significant decrease of proliferation, invasion, and ECM production in keloid fibroblasts, whereas miR-203 inhibition induced the opposite results. A dual-luciferase reporter assay identified early growth response 1 (EGR1) and fibroblast growth factor 2 (FGF2) as targets of miR-203. EGR1 and FGF2 were overexpressed in keloid fibroblasts and negatively regulated by miR-203. Furthermore, overexpression of EGR1 and FGF2 partially attenuated the suppressive effect of miR-203 on the proliferation, invasion, and ECM production of keloid fibroblasts. In conclusion, we demonstrated for the first time that miR-203 decreased the proliferation, invasion, and ECM production of keloid fibroblasts by repressing EGR1 and FGF2 expression, suggesting a potential role of miR-203 in preventing and treating keloids.