MicroRNA-519d inhibits proliferation and induces apoptosis of human hypertrophic scar fibroblasts through targeting Sirtuin 7

MicroRNAs (miRNAs) play critical roles in various pathological processes, including hypertrophic scar (HS) formation. However, the precise role of miRNAs in HS formation remains largely unknown. In this study, we aimed to investigate the role of miR-519d in HS formation. We found that miR-519d expression was significantly downregulated in HS tissues and fibroblasts. Overexpression of miR-519d inhibited the expression of type I collagen (Col I), type III collagen (Col III) and alpha-smooth muscle actin (alpha-SMA) in HS fibroblasts. Moreover, overexpression of miR-519d reduced the proliferation and induced the apoptosis of HS fibroblasts. In contrast, suppression of miR-519d showed the opposite effects. Interestingly, Sirtuin 7 (SIRT7) was identified as a target gene of miR-519d. The results showed that miR-519d directly targeted the 3'-untranslated region of SIRT7 and negatively regulated its expression. Furthermore, miR-519d regulated the expression of TGF-beta type I receptor (TGFBRI) and the phosphorylation of Smad2. Knockdown of SIRT7 by siRNA inhibited the expression of Col I, Col III and alpha-SMA, and reduced the proliferation and induced the apoptosis of HS fibroblasts. Overexpression of SIRT7 abrogated the effects mediated by miR-519d overexpression in HS fibroblasts. Overall, these results suggest that miR-519d inhibits the expression of extracellular matrix-associated genes, reduces the proliferation and induces the apoptosis of HS fibroblasts by targeting SIRT7, implying a suppressive role of miR-519d in HS formation. This study suggests that miR-519d may serve as a promising therapeutic target for treatment of human HS.