本文選題：微小R- + 小鼠胚胎成纖維細胞�。� 參考：《中國生物化學與分子生物學報》2016年11期

【摘要】：微小RNA(miRNAs)作為強大的基因表達調(diào)控子,廣泛參與多種生命過程,在細胞衰老進程中的作用也日益受到關注。miR-223是一個典型的抑癌基因,可顯著抑制細胞增殖能力。miR-223與阿爾茨海默癥、心血管疾病以及類風濕性關節(jié)炎等衰老相關疾病的發(fā)生發(fā)展密切相關。盡管如此,miR-223在細胞衰老進程中的作用及其分子機制尚未見報道。本研究通過連續(xù)傳代建立了小鼠胚胎成纖維細胞(MEF細胞)的復制性衰老模型,并利用熒光定量qRT-PCR檢測發(fā)現(xiàn),miR-223在衰老MEF細胞中的表達水平顯著上調(diào)。隨后,通過轉(zhuǎn)染miR-223模擬物Agomir-223在MEF細胞中過表達miR-223。結(jié)果顯示,過表達miR-223可顯著促進MEF細胞的衰老表型并抑制其增殖能力,而抑制miR-223的表達可延緩MEF細胞的復制性衰老進程。進一步利用生物信息學方法預測,獲得多個miR-223的候選衰老相關靶基因,包括Rasa1、Ddit4和Smad1等。然而,雙螢光素酶報告系統(tǒng)結(jié)果顯示,miR-223并不顯著影響其螢光強度,表明它們很可能并不是miR-223的下游靶基因。綜上所述,miR-223可顯著促進MEF細胞復制性衰老,然而其調(diào)節(jié)細胞衰老進程的分子機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.
【作者單位】： 廣東醫(yī)科大學衰老研究所;廣東醫(yī)科大學生物化學與分子生物學研究所;廣東省醫(yī)學分子診斷重點實驗室;
【基金】：國家自然科學基金(No.31600976,81671399,81170327) 廣東省自然科學基金(No.2014A030310027,2016A030313684) 廣東省醫(yī)學科研基金項目(No.A2015288) 廣東省攀登計劃專項資金(No.pdjh2016b0219)資助~~
【分類號】：R3416
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本文編號：2028809