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  • Title: Competing endogenous RNA network associated with oxygen-induced retinopathy: Expression of the network and identification of the MALAT1/miR-124-3p/EGR1 regulatory axis.
    Author: Xia F, Xu Y, Zhang X, Lyu J, Zhao P.
    Journal: Exp Cell Res; 2021 Nov 01; 408(1):112783. PubMed ID: 34469714.
    Abstract:
    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.
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