The expression of microRNA-451 in human endometriotic lesions is inversely related to that ofmacrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival

Abstract

study question: What is the role of microRNA-451 (miR-451) in human endometriotic tissue? summary answer: miR451 expression was elevated in endometriotic lesion tissue. MiR451 modulated the expression of macrophage migration inhibitory factor and limited cell survival. what is known already: microRNAs are post-transcriptional regulators of gene expression which have been reported to be mis-expressed in endometriotic tissue. The exact pattern of expression and role of miR451 in endometriosis is currently unknown. study design, size, duration: Thirty women with endometriosis are included in the study. participants/materials, setting, methods: Matched eutopic (N = 30) and endometriotic lesion tissue (N = 43) were collected. miR-451, macrophage migration inhibitory factor (MIF), cyclin E1 (CCNE) and phosphatase and tensin homolog (PTEN)mRNAexpressionwere examined by quantitative real-time (qRT)-PCR while MIF protein expression was evaluated bywestern blot analysis. miR-451 regulation of MIF in vitro translation was confirmed by 3-Œuntranslated region (UTR) reporter assays and western blot analysis. The effect of miR-451 on cell survival was assessed using a human endometrial epithelial cell line (HES). main results and the role of chance: Compared with eutopic endometrium, both MIF mRNA and protein were significantly (P < 0.05) decreased in endometriotic lesions and this was associated with a significant (P < 0.05) increase in miR-451 expression. Transfection of HES cells with luciferase reporter constructs for MIF revealed that miR-451 specifically bound to the 3-ŒUTR to regulate expression. Further, forced expression of miR-451 induced a significant (P < 0.05) down-regulation of both MIFmRNAand protein in HES cells which was associated with a significant (P < 0.05) reduction in cell survival. Inhibition of MIF using a specific antagonist verified that reduction of MIF contributes to HES cell survival. limitations, reasons for caution: miR-451 and MIF expression were only examined in tissue fromwomen with endometriosis. wider implications of the findings: Our data support the hypothesis that miR-451 is elevated in endometriotic tissue and, through regulating MIF expression, may function to limit endometriotic lesion cell survival. study funding/competing interest(s): This study was funded by the National Institutes of Health/NICHD by grant NIH HD069043 toW.B.N. The authors have no competing interests.