首页> 美国卫生研究院文献>Aging (Albany NY) >Competing endogenous network analysis identifies lncRNA Meg3 activates inflammatory damage in UVB induced murine skin lesion by sponging miR-93-5p/epiregulin axis
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Competing endogenous network analysis identifies lncRNA Meg3 activates inflammatory damage in UVB induced murine skin lesion by sponging miR-93-5p/epiregulin axis

机译:竞争性内源网络分析鉴定了通过刺激miR-93-5p /上皮调节蛋白轴lncRNA Meg3激活了UVB诱导的小鼠皮肤病变中的炎症损伤

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摘要

In this study, we obtained the RNA expression data of murine skin tissues of control, and UVB irradiated groups. After the re-annotation of lncRNAs, a gene expression similarity analysis was done by WGCNA. The target mRNA prediction of lncRNAs, miRNAs, and ceRNA regulatory networks were constructed by five lncRNAs, 14 miRNAs and 54 mRNAs, respectively. Based on the ceRNA network of UVB-induced skin lesions, it was evident that the dysregulation of Meg3 has critical effects on the UVB-induced inflammatory lesion of murine skin tissues. The overexpression of Meg3 after UVB irradiation was observed in primary murine skin fibroblasts, and the up-regulated Meg3 expression was related to the activation of the inflammatory cytokines. These functional experiments demonstrated that the RNA silencing of Meg3 in murine skin fibroblasts could suppress the expression of the cytokines ( ) and UVB-induced skin lesions ( . Moreover, the Meg3 functioned as a competing endogenous RNA (ceRNA) that acted as a sponge for miR-93-5p and thereby modulated the expression of Epiregulin (Ereg). Our results proved that Meg3 was involved in UVB-induced skin inflammation and that the ceRNA networks, which includes miR-93-5p and Ereg, could prove to be a potential therapeutic target for UVB-induced skin damage.
机译:在这项研究中,我们获得了对照组和UVB照射组的小鼠皮肤组织的RNA表达数据。在对lncRNA进行重新注释后,通过WGCNA进行基因表达相似性分析。 lncRNA,miRNA和ceRNA调控网络的目标mRNA预测分别由5个lncRNA,14个miRNA和54个mRNA构建。基于UVB诱导的皮肤损伤的ceRNA网络,很明显,Meg3的失调对UVB诱导的小鼠皮肤组织炎性病变具有关键作用。在原代小鼠皮肤成纤维细胞中观察到UVB照射后Meg3的过度表达,并且Meg3的表达上调与炎性细胞因子的激活有关。这些功能性实验表明,鼠皮肤成纤维细胞中Meg3的RNA沉默可以抑制细胞因子()和UVB诱导的皮肤损伤(。)的表达。此外,Meg3充当竞争性内源RNA(ceRNA)的作用miR-93-5p从而调节上皮调节蛋白(Ereg)的表达我们的结果证明Meg3参与了UVB诱导的皮肤炎症,并且包括miR-93-5p和Ereg在内的ceRNA网络可能被证明是UVB引起的皮肤损伤的潜在治疗靶标。

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