Reduced microRNA-451 expression in eutopic endometrium contributes to the pathogenesis of endometriosis

Abstract

BACKGROUND

Endometriosis (EMs) is a chronic and recurrent, but benign, disease in women of reproductive age, and EMs patients have a high risk of developing gynecological tumors and autoimmune disorders. The etiology of EMs is not clear. Certain genetic markers in the eutopic endometrium are key in the pathogenesis of EMs. MicroRNAs (miRNAs) are implicated in several biological processes, such as cell proliferation, differentiation, and apoptosis. MiR-451 is interesting, as it acts as a tumor suppressor and is relevant to the poor prognosis of cancers.

AIM

To evaluate the expression levels and role of miR-451 in the eutopic endometrium and predict possible targets of miR-451 and related signaling pathways.

METHODS

Quantitative real-time polymerase chain reaction was used to evaluate miR-451 expression in cultured cell lines as well as in pathologic tissues from 40 patients with EMs and 20 donors with no history of the disease (controls). Cell Counting Kit-8 and flow cytometric assays were performed to determine cell proliferation and survival rates after transfection with miR-451 mimics and siRNAs. MiR-451 targets were predicted using miRDB and miRcode target-predicting databases.

RESULTS

We observed lower miR-451 levels in eutopic endometrial tissues from patients with EMs than in control tissues, and this difference was not related to the American Society for Reproductive Medicine stage. Ectopic overexpression of miR-451 in eutopic cells induced apoptosis and inhibited cell proliferation. SiRNA-mediated miR-451 knockdown reversed these effects. Using miRDB and miRcode, we identified 12 potential miR-451 target genes. We hypothesize that the expression of YWHAZ, OSR1, TTN, and CDKN2D may be regulated by miR-451 and be involved in disease pathogenesis.

CONCLUSION

Reduced miR-451 expression in the eutopic endometrium contributes to the pathogenesis of EMs by promoting cell proliferation and reducing apoptosis. Thus, miR-451 is a novel biomarker for EMs. YWHAZ, OSR1, TTN, and CDKN2D are potential target genes of miR-451 and may have key roles in this disease.