MicroRNA‑486‑5p inhibits the growth of human hypertrophic scar fibroblasts by regulating Smad2 expression.

Abstract

The aim of the current study was to investigate the expression and role of microRNA-486-5p (miR-486-5p) in hypertrophic scar (HS) formation, and to examine the associated mechanisms. First, miR-486-5p expression was detected in HS tissues and human hypertrophic scar fibroblasts (hHSFs) by reverse transcription-quantitative polymerase chain reaction. Target genes of miR-486-5p were predicted using TargetScan and verified by dual-luciferase reporter assays. To investigate the role of miR-486-5p in HS formation, miR-486-5p was overexpressed in hHSFs through transfection with miR-486-5p mimics. MTT, cell apoptosis and cell cycle assays were preformed to investigate the proliferation, cell apoptosis and cell cycle distribution of hHSFs, respectively. Additionally, protein expression was measured by western blot analysis. The results demonstrated that miR-486-5p expression was significantly decreased in HS tissues and cells. Mothers against decapentaplegic homolog (Smad)2 was a target gene of miR-486-5p, and it was negatively regulated by miR-486-5p. It was also found that Smad2 expression was significantly increased in HS tissues and cells. Further analysis indicated that miR-486-5p mimic transfection inhibited the proliferation, induced cell apoptosis and increased G1/S phase arrest in hHSFs. Furthermore, the expression of cyclin-dependent kinase (CDK)2, CDK4 and apoptosis regulator Bcl-2 was repressed, while apoptosis regulator BAX expression was enhanced by miR-486-5p mimic transfection. Notably, the effects of miR-486-5p mimic on hHSFs were significantly eliminated by Smad2 plasmid transfection. Taken together, these results demonstrated that miR-486-5p inhibited the proliferation, induced apoptosis and increased G1/S phase arrest of hHSFs by targeting Smad2. miR-486-5p may be a promising therapeutic target for HS management.