학술논문

Early and late effects of aspirin and naproxen on microRNAs in the lung and blood of mice, either unexposed or exposed to cigarette smoke.
Document Type
Academic Journal
Author
Izzotti A; Department of Health Sciences, University of Genoa, Genoa, Italy.; IRCCS AOU San Martino IST, Genoa, Italy.; Balansky R; National Center of Oncology, Sofia, Bulgaria.; Ganchev G; National Center of Oncology, Sofia, Bulgaria.; Iltcheva M; National Center of Oncology, Sofia, Bulgaria.; Longobardi M; Department of Health Sciences, University of Genoa, Genoa, Italy.; Pulliero A; Department of Health Sciences, University of Genoa, Genoa, Italy.; Camoirano A; Department of Health Sciences, University of Genoa, Genoa, Italy.; D'Agostini F; Department of Health Sciences, University of Genoa, Genoa, Italy.; Geretto M; Department of Health Sciences, University of Genoa, Genoa, Italy.; Micale RT; Department of Health Sciences, University of Genoa, Genoa, Italy.; La Maestra S; Department of Health Sciences, University of Genoa, Genoa, Italy.; Miller MS; Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA.; Steele VE; Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA.; De Flora S; Department of Health Sciences, University of Genoa, Genoa, Italy.
Source
Publisher: Impact Journals Country of Publication: United States NLM ID: 101532965 Publication Model: eCollection Cited Medium: Internet ISSN: 1949-2553 (Electronic) Linking ISSN: 19492553 NLM ISO Abbreviation: Oncotarget Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
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.
Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.