MiR-101 and miR-144 regulate the expression of the CFTR chloride channel in the lung.
MiR-101 and miR-144 regulate the expression of the CFTR chloride channel in the lung.
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DOI：
10.1371/journal.pone.0050837
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cormet-Boyaka E
中科院分区：
文献类型：
--
作者：
Hassan F;Nuovo GJ;Crawford M;Boyaka PN;Kirkby S;Nana-Sinkam SP;Cormet-Boyaka E
囊性纤维化跨膜电导调节器(CFTR)是一种氯离子通道，通过维持液体平衡在肺中发挥关键作用。CFTR的缺失或功能障碍会导致囊性纤维化，这是一种以慢性感染和炎症为特征的疾病。我们最近报道，空气污染物，如香烟烟雾和镉，通过影响CFTR蛋白生物发生的几个步骤，对CFTR的表达产生负面调节。近年来，microRNAs(MiRNAs)作为生物标志物和治疗学受到了极大的关注，因为它们具有调节多个基因的能力。在这里，我们表明香烟烟雾和镉上调了两个miRNAs(miR-101和miR-144)的表达，这两个miRNAs被预测为靶向人支气管上皮细胞中的CFTR。将未成熟的miR-101和miR-144导入人呼吸道上皮细胞后，可直接靶向CFTR3‘端非编码区，并抑制CFTR3’端蛋白的表达。由于miR-101在体外被香烟烟雾高度上调，我们调查了这种上调是否也发生在体内。暴露在香烟烟雾中4周的小鼠表现出其肺中miR-101表达上调和cftr蛋白抑制。最后，我们发现与对照组相比，miR-101在严重慢性阻塞性肺疾病(COPD)患者的肺样本中高表达。综上所述，这些结果表明，慢性吸烟上调了miR-101的表达，这种miRNA可能有助于抑制COPD患者肺中CFTR的表达。
The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that plays a critical role in the lung by maintaining fluid homeostasis. Absence or malfunction of CFTR leads to Cystic Fibrosis, a disease characterized by chronic infection and inflammation. We recently reported that air pollutants such as cigarette smoke and cadmium negatively regulate the expression of CFTR by affecting several steps in the biogenesis of CFTR protein. MicroRNAs (miRNAs) have recently received a great deal of attention as both biomarkers and therapeutics due to their ability to regulate multiple genes. Here, we show that cigarette smoke and cadmium up-regulate the expression of two miRNAs (miR-101 and miR-144) that are predicted to target CFTR in human bronchial epithelial cells. When premature miR-101 and miR-144 were transfected in human airway epithelial cells, they directly targeted the CFTR 3′UTR and suppressed the expression of the CFTR protein. Since miR-101 was highly up-regulated by cigarette smoke in vitro, we investigated whether such increase also occurred in vivo. Mice exposed to cigarette smoke for 4 weeks demonstrated an up-regulation of miR-101 and suppression of CFTR protein in their lungs. Finally, we show that miR-101 is highly expressed in lung samples from patients with severe chronic obstructive pulmonary disease (COPD) when compared to control patients. Taken together, these results suggest that chronic cigarette smoking up-regulates miR-101 and that this miRNA could contribute to suppression of CFTR in the lungs of COPD patients.
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影响因子：
3.7
作者：
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影响因子：
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作者：
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通讯作者：
Boucher, R. C.
DOI：
10.1164/rccm.200508-1330oc
发表时间：
2006-05-15
影响因子：
24.7
作者：
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通讯作者：
Durie, Peter