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间充质干细胞衰老中核内miRNA表达谱特征与功能分析
作者:孟宪会1  戚宇华2  Doulathunnisa J1  孙博1 
单位:1. 东南大学 生物科学与医学工程学院/生物电子学国家重点实验室, 江苏 南京 210096;
2. 江苏省疾病预防控制中心, 江苏 南京 210009
关键词:间充质干细胞 衰老 核内微小RNA 转录调控 
分类号:R329.2;R-33
出版年·卷·期(页码):2019·38·第二期(214-223)
摘要:

目的:探讨核内微小RNA (miRNA)对间充质干细胞(MSCs)衰老的表达特征和调控作用。方法:用miRNA定量PCR芯片检测细胞核内754种miRNA在MSCs衰老前后的表达情况;通过分析差异表达最显著的核内miRNA在基因启动子区的结合位点,筛选出潜在的靶基因;对靶基因进行功能注释和信号通路分析,建立核内miRNA作用于MSCs衰老的信号调控网络。结果:270个(35.8%)核内miRNA表达在MSCs衰老后发生了显著的变化,其中209个(27.7%)miRNA呈显著上调,61个(8.1%)miRNA呈显著下调。对差异最显著核内miRNA的靶基因功能分析显示,核内miRNA参与了细胞代谢、免疫和周期等衰老相关通路的调节。结论:细胞衰老涉及核内miRNA表达谱的显著变化;核内miRNA通过基因的转录调控参与了细胞衰老关键通路的调节。

Objective:To characterize the nuclear micro RNA(miRNA) expression profiles of young and senescent MSCs and evaluate the functional mechanism of nuclear miRNAs on stem cell senescence. Methods:The expression levels of 754 miRNAs in nucleus of young and senescent MSCs were detected by a miRNA real-time PCR array. Then the miRNAs binding sites in gene promoter region were investigated and the putative target genes were identified. Finally, the target genes were annotated, the regulated signaling pathways were analyzed and the senescence-related signaling networks regulated by nuclear miRNAs were built. Results:The expressions of 270 nuclear miRNAs (35.8%) showed significant changes upon senescence of MSCs, including 209 up-regulated (27.7%) and 61 down-regulated (8.1%) miRNAs. Functional analysis of those genes targeted by the most differential nuclear miRNAs showed that nuclear miRNAs regulated signaling pathways related to metabolism, immunity and cell cycle. Conclusion:Cellular senescences involve in significant changes of nuclear miRNA expression profiles. In transcriptional level, nuclear miRNAs play key roles in regulating senescence-related signaling pathways.

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