LncRNA Gm2044 promotes 17β-estradiol synthesis in mpGCs by acting as miR-138-5p sponge
LncRNA Gm2044 promotes 17β-estradiol synthesis in mpGCs by acting as miR-138-5p sponge
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LncRNA Gm2044 通过充当 miR-138-5p 海绵促进 mpGC 中 17 β-雌二醇的合成
DOI：
10.1002/mrd.23179
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发表时间：
2019-08-01
影响因子：
2.5
通讯作者：
Liang, Meng
中科院分区：
文献类型：
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作者：
Hu, Ke;He, Chaofan;Liang, Meng
长链非编码 RNA (lncRNA) 已被证明在哺乳动物繁殖中发挥重要作用。我们前期的研究表明，lncRNA Gm2044在小鼠精母细胞中高表达，并调节雄性生殖细胞功能。基因注释数据库BioGPS显示，Gm2044不仅在睾丸组织中高表达，而且在卵巢组织中也高表达，这提示Gm2044可能参与女性生殖发育。在这项研究中，我们证实lncRNA Gm2044促进小鼠窦前卵泡颗粒细胞（mpGC）中17β-雌二醇的合成。此外，生物信息学方法、蛋白质印迹和荧光素酶测定证明，Gm2044 作为 miR-138-5p 海绵，抑制 miR-138-5p 的直接靶标 Nr5a1，从而通过 cyp19a1 激活增强 17 β-雌二醇的合成。总而言之，我们的结果提供了对 lncRNA Gm2044 通过充当竞争性内源性 RNA 来调节 mpGC 功能而对 17 β-雌二醇合成的机制作用的深入了解。研究调节雌二醇释放的潜在lncRNA将有助于类固醇激素相关疾病的诊断和治疗。
Long noncoding RNAs (lncRNAs) have been demonstrated to play vital roles in mammalian reproduction. Our previous research revealed that lncRNA Gm2044 is highly expressed in mouse spermatocytes and regulates male germ cell function. The gene annotation database BioGPS shows that Gm2044 is not only highly expressed in testicular tissue but also in ovarian tissue, which suggests that Gm2044 may be involved in female reproductive development. In this study, we confirmed that lncRNA Gm2044 promotes 17 beta-estradiol synthesis in mouse pre-antral follicular granulosa cells (mpGCs). Furthermore, bioinformatics methods, western blot, and the luciferase assay proved that Gm2044 functions as a miR-138-5p sponge to inhibit the direct target of miR-138-5p, Nr5a1, which enhances 17 beta-estradiol synthesis through cyp19a1 activation. Taken together, our results provide an insight into the mechanistic roles of lncRNA Gm2044 for 17 beta-estradiol synthesis by acting as competing-endogenous RNAs to modulate the function of mpGCs. Studying the potential lncRNAs, which regulate estradiol release, will be beneficial for the diagnosis and treatment of steroid hormone-related disease.