The expression of Mirc1/Mir17-92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients.
The expression of Mirc1/Mir17-92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients.
复制标题
MIRC1/MIR17-92在痰液样品中的表达与囊性纤维化患者的肺部恶化相关。
DOI：
10.1016/j.jcf.2017.11.005
复制
发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Amer AO
中科院分区：
文献类型：
--
作者：
Krause K;Kopp BT;Tazi MF;Caution K;Hamilton K;Badr A;Shrestha C;Tumin D;Hayes D Jr;Robledo-Avila F;Hall-Stoodley L;Klamer BG;Zhang X;Partida-Sanchez S;Parinandi NL;Kirkby SE;Dakhlallah D;McCoy KS;Cormet-Boyaka E;Amer AO
囊性纤维化是一种以慢性鼻腔肺部感染和炎症为特征的多脏器疾病。许多CF患者反复出现肺部恶化，预示着长期发病率和死亡率的恶化。目前尚无可靠的标记物与病情加重或肺恶化的发生或进展有关。此前，我们发现由6个microRNAs(MIRS)组成的Mirc1/miR17-92a簇在CF小鼠中高表达，并负向调节自噬，从而促进CF跨膜电导调节(CFTR)功能。因此，在这里，我们试图检测Mirc1/miR17-92簇中单个MIR在人类细胞和生物液中的表达，并确定它们作为肺恶化和治疗反应的生物标志物的作用。Mirc1/miR17-92簇在人的CF和非CF血浆、血液来源的中性粒细胞和痰样本中被检测到。这些值与肺功能、病情恶化和CFTR调节剂的使用有关。中性粒细胞和血浆中Mirc1/miR17-92簇的表达与非中性粒细胞相比无显著差异。CFs在痰中的表达显著高于其在血浆中的表达。CF痰Mirc1/miR17-92簇表达升高与肺加重呈正相关，与肺功能呈负相关。接受CFTR调节剂IVacaftor/Lumacaftor治疗的CF患者在治疗6个月后Mirc1/miR17-92簇的表达没有明显变化。Mirc1/miR17-92簇的表达是包括肺加重在内的CF患者呼吸状态的一个有前景的生物标志物。由Elsevier B.V.代表欧洲囊性纤维化学会出版。
Cystic fibrosis (CF) is a multi-organ disorder characterized by chronic sino-pulmonary infections and inflammation. Many patients with CF suffer from repeated pulmonary exacerbations that are predictors of worsened long-term morbidity and mortality. There are no reliable markers that associate with the onset or progression of an exacerbation or pulmonary deterioration. Previously, we found that the Mirc1/Mir17–92a cluster which is comprised of 6 microRNAs (Mirs) is highly expressed in CF mice and negatively regulates autophagy which in turn improves CF transmembrane conductance regulator (CFTR) function. Therefore, here we sought to examine the expression of individual Mirs within the Mirc1/Mir17–92 cluster in human cells and biological fluids and determine their role as biomarkers of pulmonary exacerbations and response to treatment. Mirc1/Mir17–92 cluster expression was measured in human CF and non-CF plasma, blood-derived neutrophils, and sputum samples. Values were correlated with pulmonary function, exacerbations and use of CFTR modulators. Mirc1/Mir17–92 cluster expression was not significantly elevated in CF neutrophils nor plasma when compared to the non-CF cohort. Cluster expression in CF sputum was significantly higher than its expression in plasma. Elevated CF sputum Mirc1/Mir17–92 cluster expression positively correlated with pulmonary exacerbations and negatively correlated with lung function. Patients with CF undergoing treatment with the CFTR modulator Ivacaftor/Lumacaftor did not demonstrate significant change in the expression Mirc1/Mir17–92 cluster after six months of treatment. Mirc1/Mir17–92 cluster expression is a promising biomarker of respiratory status in patients with CF including pulmonary exacerbation. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.
登录
查看更多内容
影响因子：
4.5
作者：
Grillari, Johannes;Hackl, Matthias;Grillari-Voglauer, Regina
通讯作者：
Grillari-Voglauer, Regina
影响因子：
2.2
作者：
Bernecker, C.;Halim, F.;Schott, M.
通讯作者：
Schott, M.
影响因子：
3.7
作者：
Amato F;Seia M;Giordano S;Elce A;Zarrilli F;Castaldo G;Tomaiuolo R
通讯作者：
Tomaiuolo R
影响因子：
10.3
作者：
Maisonneuve, Patrick;Marshall, Bruce C.;Lowenfels, Albert B.
通讯作者：
Lowenfels, Albert B.
影响因子：
13.3
作者：
Abdulrahman, Basant A.;Abu Khweek, Arwa;Amer, Amal O.
通讯作者：
Amer, Amal O.