Zhang Nan, Zhong Zhou, Wang Yujia, Yang Li, Wu Fengbo, Peng Cheng, Huang Wei, He Gu
State Key Laboratory of Biotherapy, Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Aging (Albany NY). 2019 Nov 24;11(22):10664-10683. doi: 10.18632/aging.102483.
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.
在本研究中,我们获取了对照组和紫外线B(UVB)照射组小鼠皮肤组织的RNA表达数据。对长链非编码RNA(lncRNAs)进行重新注释后,通过加权基因共表达网络分析(WGCNA)进行基因表达相似性分析。分别由5个lncRNAs、14个微小RNA(miRNAs)和54个信使RNA(mRNAs)构建lncRNAs、miRNAs的靶mRNA预测及竞争性内源RNA(ceRNA)调控网络。基于UVB诱导的皮肤损伤的ceRNA网络,明显可见Meg3的失调对UVB诱导的小鼠皮肤组织炎性损伤具有关键作用。在原代小鼠皮肤成纤维细胞中观察到UVB照射后Meg3的过表达,且Meg3表达上调与炎性细胞因子的激活有关。这些功能实验表明,小鼠皮肤成纤维细胞中Meg3的RNA沉默可抑制细胞因子的表达及UVB诱导的皮肤损伤。此外,Meg3作为一种竞争性内源RNA(ceRNA),充当miR-93-5p的海绵,从而调节表皮调节素(Ereg)的表达。我们的结果证明Meg3参与UVB诱导的皮肤炎症,且包括miR-93-5p和Ereg的ceRNA网络可能是UVB诱导的皮肤损伤的潜在治疗靶点。