Thymic epithelial cells (TECs) are essential regulators of T cell development and selection. microRNAs (miRNAs) play critical roles in regulating TECs proliferation during thymus involution. miR-205-5p is highly expressed in TECs and increases with age. However, the function and potential mechanism of miR-205-5p in TECs are not clear. miRNA expression was profiled using TECs from male and female mice at 1 and 3 months old. A total of 325 differentially expressed miRNAs (DEMs) were detected at different ages in two sexes. 24 of the DEMs had the same trend between males and females. Among them, miR-205-5p had the highest fold change. Our results showed that the expression of miR-205-5p was dramatically increased in TECs from 1 to 9 months old mice. miR-205-5p mimic inhibited TECs proliferation. Moreover, we confirmed that Fa2h was the direct target gene of miR-205-5p and FA2H was significantly decreased in TECs with increased expression of miR-205-5p. Silencing of Fa2h inhibited TECs proliferation. Furthermore, we found that the expression of Tfap2a could be promoted by FA2H and that TFAP2A could interact with miR-205-5p in TECs. Overall, miR-205-5p is an important regulator of TECs proliferation and regulates age-associated thymus involution via the miR-205-5p-FA2H-TFAP2A feedback regulatory circuit. miR-205-5p might act as a potential biomarker in TECs for age-related thymus involution.

中文翻译：

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miR-205-5p通过与年龄相关的胸腺退化中的FA2H-TFAP2A反馈调节来抑制胸腺上皮细胞增殖。

胸腺上皮细胞（TECs）是T细胞发育和选择的重要调节剂。microRNA（miRNA）在胸腺退化过程中调控TECs的增殖中起关键作用。miR-205-5p在TEC中高度表达，并随着年龄增长而增加。但是，miR-205-5p在TEC中的功能和潜在机制尚不清楚。使用来自1和3个月大的雄性和雌性小鼠的TEC对miRNA表达进行了分析。在不同性别的男女中共检测到325种差异表达的miRNA（DEM）。男性和女性中有24个DEM趋势相同。其中，miR-205-5p具有最高的倍数变化。我们的结果表明，从1到9个月大的小鼠中，TECs中miR-205-5p的表达显着增加。miR-205-5p模拟物抑制TECs增殖。此外，我们证实Fa2h是miR-205-5p的直接靶基因，而FA2H在TECs中随着miR-205-5p表达的增加而显着降低。Fa2h沉默可抑制TECs增殖。此外，我们发现FA2H可以促进Tfap2a的表达，而TFAP2A可以与TECs中的miR-205-5p相互作用。总体而言，miR-205-5p是TECs增殖的重要调节剂，并通过miR-205-5p-FA2H-TFAP2A反馈调节电路调节与年龄相关的胸腺退化。miR-205-5p可能是与年龄相关的胸腺退化相关的TECs的潜在生物标志物。我们发现FA2H可以促进Tfap2a的表达，而TFAP2A可以与TECs中的miR-205-5p相互作用。总体而言，miR-205-5p是TECs增殖的重要调节剂，并通过miR-205-5p-FA2H-TFAP2A反馈调节电路调节与年龄相关的胸腺退化。miR-205-5p可能是与年龄相关的胸腺退化相关的TECs的潜在生物标志物。我们发现FA2H可以促进Tfap2a的表达，而TFAP2A可以与TECs中的miR-205-5p相互作用。总体而言，miR-205-5p是TEC增殖的重要调节剂，并通过miR-205-5p-FA2H-TFAP2A反馈调节电路调节与年龄相关的胸腺退化。miR-205-5p可能是与年龄相关的胸腺退化相关的TECs的潜在生物标志物。