Inhibition of miR-23b-3p Ameliorates Scar-Like Phenotypes of Keloid Fibroblasts by Facilitating A20 Expression

Purpose: Accumulating evidence has reported that microRNAs (miRNAs) play a critical role in the mechanism of keloid formation, and recent research found that miR-23b-3p was upregulated in keloid fibroblasts (KFs). Herein, we explored the potential effect of miR-23b-3p on fibroblasts in keloid. Materials and Methods: Clinical tissues, primary KFs and KEL FIB cells were used to detect the expression of miR-23b-3p by performing qRT-PCR. Gene knockdown was carried out to evaluate the molecular and biological changes of primary KFs and KEL FIB cells by conducting CCK-8 assay, flow cytometry and Western blot. The online databases and luciferase reporter assay were utilized to screen and identify the potential target of miR-23b-3p. Results: Upregulation of miR-23b-3p was detected in keloid tissues, primary KFs and KF cell line KEL FIB cells, and inhibition of miR-23b-3p promoted apoptosis and suppressed proliferation and the expression of collagen I, collagen III and fibronectin of primary KFs and KEL FIB cells. Further investigation revealed that TNFAIP3 , the ubiquitin-editing enzyme A20, was the direct target of miR-23b-3p, and inhibition of miR-23b-3p promoted the expression of A20 in primary KFs and KEL FIB cells. The in vitro assays indicated that A20 suppression inhibited apoptosis and facilitated proliferation and the expression of collagen I, collagen III and fibronectin of miR-23b-3p inhibitor-transfected primary KFs and KEL FIB cells. Finally, we found that miR-23b-3p inhibitor reduced the expression of receptor interacting serine/threonine protein kinase 1 (RIPK1), which was partially reversed by A20 inhibition. Conclusion: These findings suggested that inhibition of miR-23b-3p/A20/RIPK1 axis induced apoptosis, limited proliferation and decreased extracellular matrix of KFs, providing a potential therapeutic target for treatment of keloid. Keywords: keloid fibroblasts, proliferation, apoptosis, extracellular matrix, MiR-23b-3p