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The expression of microRNA-451 in human endometriotic lesions is inversely related to that of macrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival.
Hum Reprod 2015; 30(3):642-52HR

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) mRNA expression were examined by quantitative real-time (qRT)-PCR while MIF protein expression was evaluated by western blot analysis. miR-451 regulation of MIF in vitro translation was confirmed by 3'untranslated 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'UTR to regulate expression. Further, forced expression of miR-451 induced a significant (P < 0.05) down-regulation of both MIF mRNA and 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 from women 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 INTERESTS

This study was funded by the National Institutes of Health/NICHD by grant NIH HD069043 to W.B.N. The authors have no competing interests.

Authors+Show Affiliations

Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA Institute for Reproductive Health and Regenerative Medicine, Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA.Department of Department of Obstetrics, Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH 44195, USA.Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA Institute for Reproductive Health and Regenerative Medicine, Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA wnothnic@kumc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25637622

Citation

Graham, Amanda, et al. "The Expression of microRNA-451 in Human Endometriotic Lesions Is Inversely Related to That of Macrophage Migration Inhibitory Factor (MIF) and Regulates MIF Expression and Modulation of Epithelial Cell Survival." Human Reproduction (Oxford, England), vol. 30, no. 3, 2015, pp. 642-52.
Graham A, Falcone T, Nothnick WB. The expression of microRNA-451 in human endometriotic lesions is inversely related to that of macrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival. Hum Reprod. 2015;30(3):642-52.
Graham, A., Falcone, T., & Nothnick, W. B. (2015). The expression of microRNA-451 in human endometriotic lesions is inversely related to that of macrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival. Human Reproduction (Oxford, England), 30(3), pp. 642-52. doi:10.1093/humrep/dev005.
Graham A, Falcone T, Nothnick WB. The Expression of microRNA-451 in Human Endometriotic Lesions Is Inversely Related to That of Macrophage Migration Inhibitory Factor (MIF) and Regulates MIF Expression and Modulation of Epithelial Cell Survival. Hum Reprod. 2015;30(3):642-52. PubMed PMID: 25637622.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The expression of microRNA-451 in human endometriotic lesions is inversely related to that of macrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival. AU - Graham,Amanda, AU - Falcone,Tommaso, AU - Nothnick,Warren B, Y1 - 2015/01/29/ PY - 2015/2/1/entrez PY - 2015/2/1/pubmed PY - 2015/11/10/medline KW - endometriosis KW - macrophage migration inhibitory factor KW - miRNA SP - 642 EP - 52 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 30 IS - 3 N2 - 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) mRNA expression were examined by quantitative real-time (qRT)-PCR while MIF protein expression was evaluated by western blot analysis. miR-451 regulation of MIF in vitro translation was confirmed by 3'untranslated 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'UTR to regulate expression. Further, forced expression of miR-451 induced a significant (P < 0.05) down-regulation of both MIF mRNA and 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 from women 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 INTERESTS: This study was funded by the National Institutes of Health/NICHD by grant NIH HD069043 to W.B.N. The authors have no competing interests. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/25637622/The_expression_of_microRNA_451_in_human_endometriotic_lesions_is_inversely_related_to_that_of_macrophage_migration_inhibitory_factor__MIF__and_regulates_MIF_expression_and_modulation_of_epithelial_cell_survival_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/dev005 DB - PRIME DP - Unbound Medicine ER -