Xu Minwen, Sizova Olga, Wang Liefeng, Su Dong-Ming
1First Affiliated Hospital, Gannan Medical University, Ganzhou 341000, China.
3Institute of Molecular Medicine, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Aging Dis. 2017 May 2;8(3):277-286. doi: 10.14336/AD.2016.1109. eCollection 2017 May.
Decline of transcription factor , which predominantly regulates thymic epithelial cell (TEC) differentiation and homeostasis lifelong, is demonstrated to be casually related to age-related thymic involution. Whereas, a global role of microRNAs (miRNAs) has also been demonstrated to control and maintain TEC-constituting thymic microenvironment and to be changed in expression profile in the aged thymus. Therefore, it is urgently necessary to build knowledge regarding whether and which miRNAs regulate gene in the aged thymus. We primarily compared changes in miRNA expression profile between young and aged murine TECs with miRBase-V20 arrays (containing 1892 unique probes), and clearly identified and validated that at least one miRNA, miR-125a-5p, was increased in aged thymus. Applying miR-125a-5p mimics was able to inhibit 3'UTR luciferase activity in a 293T cell line and to suppress FoxN1 expression in murine TEC Z210 cells. Since a single miRNA can play a fine-tuning role to regulate expression of multiple genes and a single gene can be regulated by multiple miRNAs, our result adds a single miRNA, miR-125a-5p, into the panel of -regulating miRNAs associated with thymic aging.
转录因子主要在一生中调节胸腺上皮细胞(TEC)的分化和稳态,其下降被证明与年龄相关的胸腺退化存在因果关系。然而,微小RNA(miRNA)的整体作用也已被证明可控制和维持构成TEC的胸腺微环境,并且在老年胸腺中的表达谱会发生变化。因此,迫切需要了解是否以及哪些miRNA在老年胸腺中调节基因。我们主要使用miRBase-V20阵列(包含1892个独特探针)比较了年轻和老年小鼠TEC之间miRNA表达谱的变化,并明确鉴定和验证了至少一种miRNA,即miR-125a-5p,在老年胸腺中有所增加。应用miR-125a-5p模拟物能够抑制293T细胞系中的3'UTR荧光素酶活性,并抑制小鼠TEC Z210细胞中的FoxN1表达。由于单个miRNA可以对多个基因的表达起到微调作用,且单个基因可由多个miRNA调节,我们的结果在与胸腺衰老相关的调节性miRNA中增加了单个miRNA,即miR-125a-5p。