Izzotti Alberto, Balansky Roumen, Ganchev Gancho, Iltcheva Marietta, Longobardi Mariagrazia, Pulliero Alessandra, Camoirano Anna, D'Agostini Francesco, Geretto Marta, Micale Rosanna T, La Maestra Sebastiano, Miller Mark Steven, Steele Vernon E, De Flora Silvio
Department of Health Sciences, University of Genoa, Genoa, Italy.
IRCCS AOU San Martino IST, Genoa, Italy.
Oncotarget. 2017 Aug 24;8(49):85716-85748. doi: 10.18632/oncotarget.20464. eCollection 2017 Oct 17.
We recently showed that nonsteroidal anti-inflammatory drugs (NSAIDs) are able to inhibit the lung tumors induced by cigarette smoke, either mainstream (MCS) or environmental (ECS), in female mice. We used subsets of mice to analyze the expression of 1135 microRNAs in both lung and blood serum, as related to the whole-body exposure to smoke and/or oral administration of either aspirin or naproxen. In a first study, we evaluated early microRNA alterations in A/J mice exposed to ECS for 10 weeks, starting at birth, and/or treated with NSAIDs for 6 weeks, starting after weaning. At that time, when no histopathological change were apparent, ECS caused a considerable downregulation of pulmonary microRNAs affecting both adaptive mechanisms and disease-related pathways. Aspirin and naproxen modulated, with intergender differences, the expression of microRNAs having a variety of functions, also including regulation of cyclooxygenases and inflammation. In a second study, we evaluated late microRNA alterations in Swiss H mice exposed to MCS during the first 4 months of life and treated with NSAIDs after weaning until 7.5 months of life, when tumors were detected in mouse lung. Modulation of pulmonary microRNAs by the two NSAIDs was correlated with their ability to prevent preneoplastic lesions (microadenomas) and adenomas in the lung. In both studies, exposure to smoke and/or treatment with NSAIDs also modulated microRNA profiles in the blood serum. However, their levels were poorly correlated with those of pulmonary microRNAs, presumably because circulating microRNAs reflect the contributions from multiple organs and not only from lung.
我们最近发现，非甾体抗炎药（NSAIDs）能够抑制雌性小鼠中由主流香烟烟雾（MCS）或环境香烟烟雾（ECS）诱发的肺部肿瘤。我们使用了几组小鼠来分析肺组织和血清中1135种微小RNA的表达情况，这些表达与全身暴露于烟雾和/或口服阿司匹林或萘普生有关。在第一项研究中，我们评估了从出生开始暴露于ECS 10周和/或从断奶后开始用NSAIDs治疗6周的A/J小鼠早期微小RNA的变化。那时，当没有明显的组织病理学变化时，ECS导致肺部微小RNA显著下调，影响适应性机制和疾病相关途径。阿司匹林和萘普生对具有多种功能的微小RNA的表达进行了调节，其中包括对环氧化酶和炎症的调节，且存在性别差异。在第二项研究中，我们评估了在生命的前4个月暴露于MCS并在断奶后用NSAIDs治疗直至7.5个月（此时在小鼠肺部检测到肿瘤）的瑞士H小鼠晚期微小RNA的变化。两种NSAIDs对肺部微小RNA的调节与其预防肺部癌前病变（微腺瘤）和腺瘤的能力相关。在两项研究中，暴露于烟雾和/或用NSAIDs治疗也调节了血清中的微小RNA谱。然而，它们的水平与肺部微小RNA的水平相关性较差，推测是因为循环中的微小RNA反映了多个器官的贡献，而不仅仅是肺。
