Abstract Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been identified as a regulatory molecule in angiogenesis. The goal of this study was to illustrate how MEG3 affects the angiogenesis of vascular endothelial cells. Expression of MEG3, miR-147 and intracellular cell adhesion molecule-1 (ICAM-1) in human microvascular endothelial cell line (HMEC-1) was altered by transfection, then cell viability, apoptosis, migration, tube formation, as well as the correlation among MEG3, miR-147 and ICAM-1 were explored. MEG3 was down-regulated during tube formation of HMEC-1 cells. MEG3 expression suppressed cells viability, migration and tube formation, while it induced apoptosis. MEG3 could bind with miR-147 and repress miR-147 expression. MiR-147 induced ICAM-1 expression, and contained ICAM-1 target sequences. The anti-atherogenic actions of MEG3 were inhibited by miR-147, and the anti-atherogenic actions of miR-147 suppression were also inhibited when ICAM-1 was overexpressed. Further, ICAM-1 overexpression showed activated roles in Wnt/β-catenin and Jak/Stat signaling pathways. In low-density lipoprotein receptor (Ldlr)−/− mice, MEG3 overexpression reduced CD68+, CD3+ and ICAM-1 areas in lesions and increased collagen content. MEG3 inhibited HMEC-1 cell growth, migration and tube formation. The anti-atherogenic actions of MEG3 might be mediated via sponging miR-147, and thereby repressing the expression of ICAM-1.

中文翻译：

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LncRNA MEG3 通过海绵 miR-147 抑制 HMEC-1 细胞生长、迁移和管形成

摘要 长链非编码 RNA (lncRNA) 母源表达基因 3 (MEG3) 已被鉴定为血管生成中的调控分子。本研究的目的是说明 MEG3 如何影响血管内皮细胞的血管生成。MEG3、miR-147和细胞内细胞粘附分子-1（ICAM-1）在人微血管内皮细胞系（HMEC-1）中的表达被转染改变，然后细胞活力、凋亡、迁移、管形成，以及探讨了 MEG3、miR-147 和 ICAM-1 之间的相关性。MEG3 在 HMEC-1 细胞的管形成过程中被下调。MEG3 表达抑制细胞活力、迁移和管形成，同时诱导细胞凋亡。MEG3 可以与 miR-147 结合并抑制 miR-147 的表达。MiR-147 诱导 ICAM-1 表达，并含有 ICAM-1 靶序列。MEG3的抗动脉粥样硬化作用被miR-147抑制，当ICAM-1过表达时，miR-147抑制的抗动脉粥样硬化作用也被抑制。此外，ICAM-1 过表达在 Wnt/β-catenin 和 Jak/Stat 信号通路中显示出激活的作用。在低密度脂蛋白受体 (Ldlr)-/- 小鼠中，MEG3 过表达减少了病变中的 CD68+、CD3+ 和 ICAM-1 区域并增加了胶原蛋白含量。MEG3 抑制 HMEC-1 细胞生长、迁移和管形成。MEG3 的抗动脉粥样硬化作用可能是通过海绵 miR-147 介导的，从而抑制 ICAM-1 的表达。ICAM-1 过表达在 Wnt/β-catenin 和 Jak/Stat 信号通路中显示出激活的作用。在低密度脂蛋白受体 (Ldlr)-/- 小鼠中，MEG3 过表达减少了病变中的 CD68+、CD3+ 和 ICAM-1 区域并增加了胶原蛋白含量。MEG3 抑制 HMEC-1 细胞生长、迁移和管形成。MEG3 的抗动脉粥样硬化作用可能是通过海绵 miR-147 介导的，从而抑制 ICAM-1 的表达。ICAM-1 过表达在 Wnt/β-catenin 和 Jak/Stat 信号通路中显示出激活的作用。在低密度脂蛋白受体 (Ldlr)-/- 小鼠中，MEG3 过表达减少了病变中的 CD68+、CD3+ 和 ICAM-1 区域并增加了胶原蛋白含量。MEG3 抑制 HMEC-1 细胞生长、迁移和管形成。MEG3 的抗动脉粥样硬化作用可能是通过海绵 miR-147 介导的，从而抑制 ICAM-1 的表达。