Guo Pan, Huang Junkai, Zhang Jing, Meng Chao, Zhang Shuchang, Bai Yunfeng, Ning Zhiwei, Hu Lizhi
Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University Tianjin 300070 China
Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University Tianjin 300070 China.
RSC Adv. 2019 Jun 18;9(33):19095-19103. doi: 10.1039/c9ra02322d. eCollection 2019 Jun 14.
/: Mediator complex subunit 1 (MED1) is an important transcriptional co-activator involved in multiple signaling pathways. Previous studies indicated an essential role of MED1 in hair cycling and wound repair through regulating the transcription of mRNAs. Circular RNAs (circRNAs), as a novel class of non-coding RNAs, are involved in various skin biological functions. Our study aimed to investigate the circRNAs expression profile in MED1 epidermal conditional knockout mice (KO), and provide potential candidates as well as the mechanism underlying the circRNAs regulation in both hair follicles and epidermis. : Microarray based circRNA expression was determined in MED1 KO mice and wild type mice (WT). The expression level was further confirmed by qRT-PCR. We predicted a possible interaction network of circRNA/microRNA/mRNA by bioinformatics and constructed them with Cytoscape software. Expression of several candidate target mRNAs was verified using qRT-PCR. A TUNEL assay was performed to assess the apoptosis level of MED1 KO and WT skin. : Here we identified 109 (34-up, 75-down) distinct circRNAs through microarrays that are differently expressed in MED1 KO mice compared with WT mice (FC > 2 and -value < 0.05), suggesting a potential role of circRNAs in epidermal regulation. Among these circRNAs, circRNA_004229 was found to decrease significantly after MED1 deletion. The most likely potential targets miRNA for circRNA_004229 include miR-149-5p and miR-207, which possibly further impede the expression of their target mRNA, Tnfrsf19 and Perp, respectively. Apoptosis was suppressed in MED1 KO mice, which implies a potential role of circRNAs in regulating epidermal biological processes including apoptosis. : Our study determined the expression profile of circRNAs in MED1 KO skin, and provided hints that circRNA_004229 might be involved in the regulation of keratinocytes in both hair follicles and interfollicular epidermis through a ceRNA mechanism.
中介体复合物亚基1(MED1)是一种重要的转录共激活因子,参与多种信号通路。先前的研究表明,MED1通过调节mRNA的转录在毛发周期和伤口修复中起重要作用。环状RNA(circRNAs)作为一类新型的非编码RNA,参与各种皮肤生物学功能。我们的研究旨在调查MED1表皮条件性敲除小鼠(KO)中circRNAs的表达谱,并提供潜在的候选分子以及circRNAs在毛囊和表皮中调控的潜在机制。通过微阵列确定MED1 KO小鼠和野生型小鼠(WT)中基于微阵列的circRNA表达。通过qRT-PCR进一步确认表达水平。我们通过生物信息学预测了circRNA/微小RNA/信使RNA的可能相互作用网络,并用Cytoscape软件构建了它们。使用qRT-PCR验证了几种候选靶信使RNA的表达。进行TUNEL分析以评估MED1 KO和WT皮肤中的细胞凋亡水平。在这里,我们通过微阵列鉴定了109个(34个上调,75个下调)不同的circRNAs,与WT小鼠相比,它们在MED1 KO小鼠中差异表达(FC>2且p值<0.05),表明circRNAs在表皮调控中具有潜在作用。在这些circRNAs中,发现circRNA_004229在MED1缺失后显著降低。circRNA_004229最可能的潜在靶微小RNA包括miR-149-5p和miR-207,它们可能分别进一步阻碍其靶信使RNA Tnfrsf19和Perp的表达。MED1 KO小鼠中的细胞凋亡受到抑制,这意味着circRNAs在调节包括细胞凋亡在内的表皮生物学过程中具有潜在作用。我们的研究确定了MED1 KO皮肤中circRNAs的表达谱,并提示circRNA_004229可能通过ceRNA机制参与毛囊和毛囊间表皮中角质形成细胞的调控。