The potential role of circRNA_004229 in hair/epidermal regulation after MED1 ablation in keratinocytes.
The potential role of circRNA_004229 in hair/epidermal regulation after MED1 ablation in keratinocytes.
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角质形成细胞MED1消融后circRNA_004229在头发/表皮调节中的潜在作用
作者：
背景/目的：介导复合体亚基 1 (MED1) 是参与多种信号转导通路的重要转录共激活因子。先前的研究表明 MED1 通过调节 mRNA 的转录在毛发循环和伤口修复中发挥重要作用。环状RNA（circRNA）作为一类新型非编码RNA，参与多种皮肤生物学功能。我们的研究旨在研究MED1表皮条件敲除小鼠（KO）中的circRNA表达谱，并提供潜在的候选者以及毛囊和表皮中circRNA调节的机制。方法：在 MED1 KO 小鼠和野生型小鼠 (WT) 中测定基于微阵列的 circRNA 表达。通过qRT-PCR进一步证实表达水平。我们通过生物信息学预测了circRNA/microRNA/mRNA可能的相互作用网络，并利用Cytoscape软件构建了它们。使用 qRT-PCR 验证了几种候选靶标 mRNA 的表达。进行 TUNEL 测定来评估 MED1 KO 和 WT 皮肤的凋亡水平。结果：在这里，我们通过微阵列鉴定了 109 个（上 34 个，下 75 个）不同的 circRNA，与 WT 小鼠相比，它们在 MED1 KO 小鼠中表达不同（FC > 2 且 p 值 < 0.05），表明 circRNA 在表皮调节中的潜在作用。在这些 circRNA 中，发现 circRNA_004229 在 MED1 删除后显着减少。 circRNA_004229 最有可能的潜在靶标 miRNA 包括 miR-149-5p 和 miR-207，它们可能分别进一步阻碍其靶标 mRNA Tnfrsf19 和 Perp 的表达。 MED1 KO 小鼠中细胞凋亡受到抑制，这意味着 circRNA 在调节包括细胞凋亡在内的表皮生物过程中具有潜在作用。结论：我们的研究确定了MED1 KO皮肤中circRNA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角质形成细胞的调节。
Background/Aims: 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. Method: 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. Results: 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 p-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. Conclusion: 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.
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