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
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
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DOI：
10.1093/humrep/dev005
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发表时间：
2015-03-01
影响因子：
6.1
通讯作者：
Nothnick, Warren B.
中科院分区：
文献类型：
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作者：
Graham, Amanda;Falcone, Tommaso;Nothnick, Warren B.
研究问题：microRNA-45 I（miR-45 I）在人类乳腺癌组织中的作用是什么？总结回答：子宫内膜异位病变组织中miR 45 I表达升高。MiR 451调节巨噬细胞移动抑制因子的表达并限制细胞存活。已知：microRNA是基因表达的转录后调节因子，据报道其在增生组织中被错误表达。miR 45 I在子宫内膜异位症中的确切表达模式和作用目前尚不清楚。研究设计、规模、持续时间：30例子宫内膜异位症患者被纳入研究。通过定量实时（qRT）-PCR检测miR-451、巨噬细胞移动抑制因子（MW）、细胞周期蛋白El（CCNE）和磷酸酶和张力蛋白同源物（PTEN）mRNA表达，而通过蛋白质印迹分析评估MIF蛋白表达。通过3 '非转录区（UTR）报告基因分析和western blot分析证实miR-45 I对MIF体外翻译的调控作用。主要结果和机会的作用：与在位子宫内膜相比，增生性病变中MIF mRNA和蛋白表达均显著降低（P < 0.05），这与miR-451表达显著增加（P <0.05）相关。用MIF的荧光素酶报告基因构建体转染HES细胞，发现miR-45 I特异性结合于3 'UTR以调节表达。此外，miR-45 I的强制表达诱导了HES细胞中MIF mRNA和蛋白的显著（P < 0.05）下调，这与细胞存活率的显著降低（P < 0.05）相关。使用特异性拮抗剂抑制MIF证实了MIF的减少有助于HES细胞的存活。限制，预防的原因：miR-451和MIF的表达仅在子宫内膜异位症妇女的组织中进行了检查。研究结果的更广泛意义：我们的数据支持这样的假设，即miR-451在增生组织中升高，并且通过调节MIF表达，可能起到限制增生病变细胞存活的作用。
STUDY QUESTION: What is the role of microRNA-45 I (miR-45 I) in human endometriotic tissue?SUMMARY ANSWER: miR45 I 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 miR45 I 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 (MW), cyclin El (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-45 I regulation of MIF in vitro translation was confirmed by 3'untran slated 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-45 I specifically bound to the 3'UTR to regulate expression. Further, forced expression of miR-45 I 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.