miR-223促进小鼠胚胎成纤维细胞复制性衰老

发布时间：2018-06-17 00:46

  本文选题：微小R- + 小鼠胚胎成纤维细胞　； 参考：《中国生物化学与分子生物学报》2016年11期

【摘要】：微小RNA(miRNAs)作为强大的基因表达调控子,广泛参与多种生命过程,在细胞衰老进程中的作用也日益受到关注。miR-223是一个典型的抑癌基因,可显著抑制细胞增殖能力。miR-223与阿尔茨海默症、心血管疾病以及类风湿性关节炎等衰老相关疾病的发生发展密切相关。尽管如此,miR-223在细胞衰老进程中的作用及其分子机制尚未见报道。本研究通过连续传代建立了小鼠胚胎成纤维细胞(MEF细胞)的复制性衰老模型,并利用荧光定量qRT-PCR检测发现,miR-223在衰老MEF细胞中的表达水平显著上调。随后,通过转染miR-223模拟物Agomir-223在MEF细胞中过表达miR-223。结果显示,过表达miR-223可显著促进MEF细胞的衰老表型并抑制其增殖能力,而抑制miR-223的表达可延缓MEF细胞的复制性衰老进程。进一步利用生物信息学方法预测,获得多个miR-223的候选衰老相关靶基因,包括Rasa1、Ddit4和Smad1等。然而,双萤光素酶报告系统结果显示,miR-223并不显著影响其萤光强度,表明它们很可能并不是miR-223的下游靶基因。综上所述,miR-223可显著促进MEF细胞复制性衰老,然而其调节细胞衰老进程的分子机制依然有待深入研究。
[Abstract]:As a powerful gene expression regulator, miRNAs) is widely involved in a variety of life processes. The role of miR-223 in cell senescence is a typical tumor suppressor gene, which can significantly inhibit the proliferation of cells .miR-223 and Alzheimer's disease. The occurrence and development of aging related diseases such as cardiovascular disease and rheumatoid arthritis are closely related. However, the role of miR-223 in the process of cell senescence and its molecular mechanism have not been reported. In this study, the model of mouse embryonic fibroblast (MEF) was established by continuous subculture, and the expression level of miR-223 was significantly up-regulated in aging MEF cells by fluorescence quantitative qRT-PCR. Subsequently, miR-223 mimetic Agomir-223 was overexpressed in MEF cells. The results showed that overexpression of miR-223 could significantly promote the senescence phenotype and inhibit the proliferation of MEF cells, while inhibiting the expression of miR-223 could delay the process of replicative senescence of MEF cells. Further more, bioinformatics method was used to predict the candidate senescence related target genes of miR-223, including Rasa1 Ddit4 and Smad1. However, the results of the double luciferase reporting system showed that miR-223 did not significantly affect its fluorescence intensity, suggesting that they were probably not downstream target genes of miR-223. In conclusion, miR-223 can significantly promote the replicative senescence of MEF cells, but its molecular mechanism of regulating cellular senescence still needs to be further studied.
【作者单位】： 广东医科大学衰老研究所;广东医科大学生物化学与分子生物学研究所;广东省医学分子诊断重点实验室;
【基金】：国家自然科学基金(No.31600976,81671399,81170327) 广东省自然科学基金(No.2014A030310027,2016A030313684) 广东省医学科研基金项目(No.A2015288) 广东省攀登计划专项资金(No.pdjh2016b0219)资助~~
【分类号】：R3416
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本文编号：2028809