Reduction of microRNA-206 contributes to the development of bronchopulmonary dysplasia through up-regulation of fibronectin 1.

Reduction of microRNA-206 contributes to the development of bronchopulmonary dysplasia through up-regulation of fibronectin 1.
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MicroRNA-206 的减少通过上调纤连蛋白 1 促进支气管肺发育不良的发生

DOI:
10.1371/journal.pone.0074750
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Feng Z
Feng Z
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang X;Xu J;Wang J;Gortner L;Zhang S;Wei X;Song J;Zhang Y;Li Q;Feng Z

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探讨microRNA-206(miR-206)在支气管肺发育不良(BPD)发生发展中的作用。我们通过定量实时PCR评估miR-206在BPD小鼠肺组织和BPD患者血液样品中的表达。采用XTT法、流式细胞术、transwell侵袭实验、创伤愈合实验和体外粘附实验检测miR-206对细胞生物学的调节作用。采用荧光素酶报告基因检测、实时荧光定量PCR、免疫印迹和免疫荧光染色等方法检测miR-206的靶基因。与对照组相比,在BPD小鼠中观察到miR-206的表达减少,并且与对照组相比,在BPD患者中观察到miR-206的表达减少。miR-206过表达可显著诱导细胞凋亡,降低细胞增殖、迁移和粘附能力,而抑制miR-206表达则具有相反的作用。纤连蛋白1(FN 1)是miR-206的直接靶点,并且FN 1可以由miR-206在转录和转录上调节。miR-206的下调至少部分地通过增加fn 1的水平来调节细胞的生物学功能。此外,BPD小鼠和BPD患者的fn 1表达水平均升高. miR-206及其靶基因fn 1的表达可能参与了BPD的进展。
To characterize microRNA-206 (miR-206) in the development of bronchopulmonary dysplasia (BPD). We assessed the expression of miR-206 in BPD mouse lung tissues and blood samples of BPD patients by quantitative real-time PCR. Then, the role of miR-206 in regulating cell biology were examined by XTT assay, flow cytometry, transwell invasion assay, wound healing assay and adhesion assay in vitro. Furthermore, luciferase reporter assay, real-time PCR, western blot and Immunofluorescence staining were performed to figure out the target gene of miR-206. A reduction in expression of miR-206 was observed in BPD mice compared with controls and in BPD patients compared with controls. miR-206 overexpression significantly induced cell apoptosis, reduced cell proliferation, migration and adhesion abilities, whereas the inhibition of miR-206 expression had the opposite effect. Fibronectin 1 (FN1) is a direct target of miR-206, and fn 1 can be transcriptionally and translationally regulated by miR-206. Down-regulation of miR-206 modulates biological functions of the cells, at least in part, by increasing the level of fn 1. Furthermore, fn 1 expression levels were increased in the BPD mice and BPD patients. The expression of miR-206 and its target gene, fn 1, may contribute to the progression of BPD.
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