中文摘要：

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。

英文摘要：

MicroRNAs （miRNAs） have emerged as critical regulators of gene expression, and are involved in multiple biological processes, including cellular senescence, miR-223 has previously been demonstrated to exert an anti-proliferation effect in various human cancers, and thus serves as a typical tumor suppressor, miR-223 was closely associated with several aging-related disease, such as Alzheimer disease, cardiovascular disease and rheumatoid arthritis. Nonetheless, the association between miR-223 and cellular senescence and its underlying molecular mechanism is far to be elucidated. In this study, we established the replicative senescence model of mouse embryonic fbroblasts（MEFs） to shed light on the effect of miR-223 on cellular senescence and the potential mechanisms. Our results uncovered that miR- 223 were dramatically up-regulated in senescent MEFs（P9 MEFs） compared to the young MEF cells（P3 MEFs）. Moreover, enforced expression of miR-223 significantly promoted the replicative senescence of MEFs and decreased the proliferation capability in MEFs, while knock-down of miR-223 signifcantly delayed the replicative senescence of MEF ceils. We further predicted several aging-related candidate target genes of miR-223 utilizing bioinformatics analysis, including Rasal, Ddit4 and Smadl. However, the dual lnciferase reporter system （DLR） unveiled that miR-223 did not significant impact on the luciferase activity, indicating that Rasal, Ddit4 and Smadl might not be the authentic targets of miR- 223. In summary, the present study provided evidences that miR-223 served as a novel regulator of cellular senescence in MEFs; nonetheless, the underlying molecular mechanism of the effect of miR-223 in the replicative senescence still required further investigation.