Competing endogenous RNA network associated with oxygen-induced retinopathy: Expression of the network and identification of the MALAT1/miR-124-3p/EGR1 regulatory axis
Competing endogenous RNA network associated with oxygen-induced retinopathy: Expression of the network and identification of the MALAT1/miR-124-3p/EGR1 regulatory axis
复制标题
与氧诱导的视网膜病变相关的竞争性内源性 RNA 网络：网络的表达和 MALAT1/miR-124-3p/EGR1 调节轴的识别。
DOI：
10.1016/j.yexcr.2021.112783
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发表时间：
2021
影响因子：
3.7
通讯作者：
Zhao Peiquan
中科院分区：
文献类型：
--
作者：
Xia Fengjie;Xu Yu;Zhang Xiang;Lyu Jiao (共通）;Zhao Peiquan
早产儿视网膜病变(ROP)是早产儿严重的视网膜功能障碍。非编码RNA与早产儿视网膜病变(ROP)的关系尚不清楚。在ROP小鼠模型中进行了lncRNAs、miRNAs和mRNAs的微阵列分析。构建了竞争内源RNA(CERNA)网络。在低氧诱导的原代人脐静脉内皮细胞(HUVECs)和ROP小鼠模型中，研究MALAT1、miR-124-3p和早期生长反应蛋白1(Egr1)之间的关系。在研究中，我们发现2252个lncRNAs、1239个mRNAs和36个miRNAs被差异调控。建立了由21个lncRNAs、10个miRNAs和19个mRNAs组成的CERNA网络。在下调最多的miRNAs中，miR-124-3p被选为进一步的研究。MiR-124-3p阻断缺氧条件下原代HUVEC的迁移和增殖，并直接抑制Egr1。此外，MALAT1还直接海绵作用于miR-124-3p。MALAT1基因敲除后，原代培养的HUVEC在低氧条件下Egr1表达下降，迁移和增殖受到抑制。此外，miR-124-3p的缺失挽救了这些改变。在体内，玻璃体内注射miR-124-3p，shMALAT1降低了Egr1的表达，并显著抑制了OIR模型的视网膜新生血管。同时玻璃体内注射shMALAT1和miR-124-3p可促进视网膜新生血管，从而逆转shMALAT1抑制视网膜新生血管的作用。总之，在ROP小鼠模型中，lncRNAs和miRNAs以及Cerna网络的表达谱可能预示了视网膜血管生成和神经活动的潜在机制。MALAT1/miR-124-3p/Egr1调节轴参与了视网膜新生血管的形成，可能为ROP的发病机制提供新的理论基础。
Retinopathy of prematurity (ROP) is a severe retinal dysfunction in prematurely born babies. The relationship between non-coding RNAs and retinopathy of prematurity (ROP) remain unclear. Microarray analysis of lncRNAs, miRNAs, and mRNAs was conducted in a mouse model of ROP. A competing endogenous RNA (ceRNA) network was constructed. The relationship among MALAT1, miR-124–3p, and Early growth response protein 1 (EGR1) was assessed in hypoxia-induced primary human umbilical vein endothelial cells (HUVECs) and ROP mouse model. In the study, we found 2252 lncRNAs, 1239 mRNAs, and 36 miRNAs were differentially regulated. ceRNA network consisting of 21 lncRNAs, 10 miRNAs, and 19 mRNAs was established. Of the most down-regulated miRNAs, miR-124–3p was selected for additional study. miR-124–3p ceased the migration and proliferation of primary HUVECs in hypoxic conditions, and directly suppressed EGR1. Additionally, MALAT1 directly sponged miR-124–3p. Knockdown of MALAT1 decreased EGR1 expression and inhibited the migration and proliferation of primary HUVECs in hypoxia. Furthermore, these changes were rescued by depletion of miR-124–3p. In vivo, intravitreal injection of miR-124–3p, shMALAT1 decreased EGR1 expression and markedly suppressed retinal neovascularization in OIR models. Intravitreal injection of shMALAT1 and miR-124–3p antagomir at the same time can promote retinal neovascularization, which reversed the suppression of retinal neovascularization functioned by shMALAT1. In conclusion, the expression profiles of lncRNAs and miRNAs and the ceRNA network in a mouse model of ROP may be indicative of the underlying mechanisms of retinal angiogenesis and neural activity. The MALAT1/miR-124–3p/EGR1 regulatory axis is partly responsible for retinal neovascularization, which may provide a novel theoretical basis for the pathogenesis of ROP.