miR­455 targets FABP4 to protect human endometrial stromal cells from cytotoxicity induced by hydrogen peroxide.

Oxidative stress and dysregulation of antioxidant systems are associated with various complications in pregnancy. Endometriosis is a common gynecologic disease that affects women of reproductive age. Recent studies have indicated that oxidative stress may be involved in the pathophysiology of endometriosis. It has been reported that microRNAs can regulate the cellular response to oxidative stress, and mounting evidence indicates that fatty acid binding protein 4 (FABP4) plays an essential role in the regulation of systemic redox capacity. In the present study, we demonstrated that miR­455 is a putative FABP4­targeting miRNA. A luciferase activity assay revealed that miR­455 can successfully bind to the 3'­UTR of FABP4. Overexpression of miR­455 led to the downregulation of FABP4 at both the mRNA and protein levels in a human endometrial stromal cell line. Then, the roles of miR­455 and FABP4 in oxidative stress induced by hydrogen peroxide (H2O2) in human endometrial stromal cells were examined. We found that ectopic expression of miR­455 protected cells from damage caused by H2O2. Further investigation found that forced expression of miR­455 reduced the level of reactive oxygen species (ROS) and malondialdehyde (MDA), while the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH­Px) were promoted. Silencing of FABP4 also generated cytoprotective effects against H2O2 in human endometrial stromal cells. Moreover, overexpression FABP4 abrogated the miR­455­mediated antioxidative stress effects in cells. Taken together, we propose that miR­455 protects human endometrial stromal cells from oxidative stress at least partly via regulation of FABP4.