Long non-coding RNA366.2 controls endometrial epithelial cell proliferation and migration by upregulating WNT6 as a ceRNA of miR-1576 in sheep uterus
Long non-coding RNA366.2 controls endometrial epithelial cell proliferation and migration by upregulating WNT6 as a ceRNA of miR-1576 in sheep uterus
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长非编码RNA366.2通过上调WNT6作为绵羊子宫中miR-1576的ceRNA来控制子宫内膜上皮细胞增殖和迁移
DOI：
10.1016/j.bbagrm.2020.194606
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发表时间：
2020-09-01
影响因子：
4.7
通讯作者：
Wang, Feng
中科院分区：
文献类型：
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作者：
Gao, Xiaoxiao;Yao, Xiaolei;Wang, Feng
长链非编码RNA（lncRNA）在哺乳动物的繁殖力中发挥着重要的调节作用。目前，大多数研究主要集中在卵巢lncRNA上，忽略了子宫lncRNA对母羊繁殖力的影响。在本研究中，我们发现高繁殖力组湖羊的子宫腺体密度和子宫内膜微血管密度（MVD）高于低繁殖力组（p < 0.05），并且血清胎盘生长因子（PLGF）水平升高。通过RNA测序（RNA-seq）在不同生育力湖羊中鉴定出数百个差异表达（DE）lncRNA，其靶标富集于一些涉及子宫内膜功能的信号通路，如雌激素信号通路、核因子κB（NF-kappa B）信号通路、催产素信号通路和Wnt信号通路。此外，通过生物信息学分析确定了lncRNA366.2-miR-1576-WNT6竞争性内源RNA（ceRNA）的潜在机制。从功能上讲，我们的结果表明，lncRNA366.2 通过海绵 miR-1576 上调 WNT6 表达并激活 Wnt/β-catenin 通路，促进子宫内膜上皮细胞 (EEC) 增殖、迁移和生长因子表达。综上所述，我们的研究表明了lncRNA366.2-miR-1576-WNT6在EEC增殖和迁移中的调节机制。此外，本研究为繁殖力相关候选基因的鉴定提供了新的理论参考。
Long non-coding RNAs (lncRNAs) play an important regulatory role in mammalian fecundity. Currently, most studies are primarily concentrated on ovarian lncRNAs, ignoring the influence of uterine lncRNAs on the fecundity of female sheep. In this study, we found a higher density of uterine glands and endometrial microvessel density (MVD) in high prolificacy group of Hu sheep compared to low prolificacy groups (p < 0.05) as well as an increased level of serum placental growth factor (PLGF). Hundreds of differentially expressed (DE) lncRNAs were identified in Hu sheep with different fecundity by RNA sequencing (RNA-seq), and their targets were enriched in some signaling pathways involved in endometrial functions, such as the estrogen signaling pathway, nuclear factor kappa B (NF-kappa B) signaling pathway, oxytocin signaling pathway, and Wnt signaling pathway. Furthermore, the underlying mechanisms of competitive endogenous RNA (ceRNA) of lncRNA366.2-miR-1576-WNT6 were determined by bioinformatics analysis. Functionally, our results indicated that lncRNA366.2 promoted endometrial epithelial cell (EEC) proliferation, migration, and growth factor expression by sponging miR-1576 to upregulate WNT6 expression and activate the Wnt/beta-catenin pathway. Taken together, our research indicated the regulatory mechanism of the lncRNA366.2-miR-1576-WNT6 in EEC proliferation and migration. Furthermore, this study provides a new theoretical reference for the identification of candidate genes related to fecundity.