A novel regulatory function for miR-217 targetedly suppressing fibronectin expression in keloid fibrogenesis

Fibronectin (FN) plays a critical role in the development and progression of keloid scarring (KS). In the present study, we hypothesized that a post-translational mechanism of microRNAs regulated the expression of FN in keloid scarring fibroblasts (KSFBs). Here, we collected 20 KS tissues and paired corresponding adjacent normal tissues from clinical patients and measured the expression of miRNA-217. First, by using PicTar, TargetScan and miRBase database, we found that miRNA-217 might be a regulator of FN in human species. Based on these hypotheses, the expression of miRNA-217 and FN in KS tissues was investigated. The results demonstrated that the expression of miRNA-217 was greatly suppressed, and FN was increased in KS tissues. Intriguingly, the expression levels of endogenous miRNA-217 negatively correlated with the FN mRNA levels (Pearson's correlation coefficient = -0.683, P < 0.001). In vitro, miRNA-217 could regulate FN through the predicted binding sites in its 3'-UTR. miRNA-217 played an impact on cell proliferation and apoptosis, thereby regulating KSFBs growth. Moreover, miRNA-217 gain-of function decreased FN, Col-1 and Col-3 protein expression, and miRNA-217 loss-of function increased FN, Col-1 and Col-3 protein expression in KSFBs. In conclusion, overexpressed miRNA-217 could inhibit KSFBs growth, and the underlying mechanism was mediated, at least partially, through the suppression of FN expression. But above all, miRNA-217 might play a potential therapeutic avenue for the treatment of keloid fibrogenesis.