Mingxi Li; Haiyan Qin; Lingfeng Pan; Guang Zhang; Liehao Yang; Changcai Zhou; Caihong Li; Zichao Wang & Lianbo Zhang

Keloid scar is a unique benign fibroproliferative tumor of the human skin. Previously, it was reported that early growth response 1 (EGR1), a transcription factor, promotes keloid fibrosis; however, the mechanism by which EGR1 modulates keloid formation was not elaborated. In this research, the specific function and the microRNA (miRNA) regulatory network of EGR1 in keloids was examined. Keloid fibroblasts (KFs) were transfected with EGR1-small interfering RNA (siEGR1), EGR1-overexpression plasmid (pcDNA3.1-EGR1), and microRNA (miR-183-5p)-mimics to regulate the expression of EGR1 and miR-183-5p. The study employed dual-luciferase reporter assays to explore the targeting regulation of miR-183-5p on EGR1. Additionally, Western blotting, flow cytometry, qRT-PCR, cell count kit-8 (CCK-8), transwell, and wound healing assays, and RNA sequencing were conducted. EGR1 was upregulated in KFs, and EGR1 silencing diminished proliferation, fibrosis, migration, invasion, and apoptosis of cells. In KFs, the expression of miR- 183-5p was reduced, leading to the inhibition of cell proliferation, migration, and invasion. Conversely, it enhanced apoptosis. By targeting EGR1, miR-183-5p partially counteracted the impact of EGR1 on migration, invasion, and fibrosis in KFs. The findings imply that miR-183-5p suppresses keloid formation by targeting EGR1. As a result, EGR1 holds promise as a potential therapeutic target for preventing and treating keloids.

KEY WORDS: miR-183-5p; Keloid fibroblast; EGR1; Fibrosis.

LI, M.; QIN, H.; PAN, L.; ZHANG, G.; YANG, L.; ZHOU, C.; LI, C.; WANG, Z. & ZHANG, L. Inhibition of proliferation, migration, and invasion of keloid fibroblasts by miR-183-5p through downregulating EGR1. Int. J. Morphol., 41(6):1610-1619, 2023.