Smoke-induced microRNA and related proteome alterations. Modulation by chemopreventive agents

Dysregulation of microRNAs (miRNAs) has important consequences on gene and protein expression since a single miRNA targets a number of genes simultaneously. This article provides a review of published data and ongoing studies regarding the effects of cigarette smoke (CS), either mainstream (MCS) or...

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Bibliographic Details
Published in:International journal of cancer 2012-12, Vol.131 (12), p.2763-2773
Main Authors: De Flora, Silvio, Balansky, Roumen, D'Agostini, Francesco, Cartiglia, Cristina, Longobardi, Mariagrazia, Steele, Vernon E., Izzotti, Alberto
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Anticarcinogenic Agents - pharmacology
Biological and medical sciences
Biomarkers - metabolism
Cancer
chemopreventive agents
Chemotherapy
cigarette smoke
DNA repair
Genes
Humans
Medical research
Medical sciences
Mice
MicroRNAs
MicroRNAs - genetics
Proteome
Proteomics
Rats
Smoke - adverse effects
Smoking
Tobacco, tobacco smoking
Toxicology
Tumors
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Summary:Dysregulation of microRNAs (miRNAs) has important consequences on gene and protein expression since a single miRNA targets a number of genes simultaneously. This article provides a review of published data and ongoing studies regarding the effects of cigarette smoke (CS), either mainstream (MCS) or environmental (ECS), on the expression of miRNAs and related proteins. The results generated in mice, rats, and humans provided evidence that exposure to CS results in an intense dysregulation of miRNA expression in the respiratory tract, which is mainly oriented in the sense of downregulation. In parallel, there was an upregulation of proteins targeted by the downregulated miRNAs. These trends reflect an attempt to defend the respiratory tract by means of antioxidant mechanisms, detoxification of carcinogens, DNA repair, anti‐inflammatory pathways, apoptosis, etc. However, a long‐lasting exposure to CS causes irreversible miRNA alterations that activate carcinogenic mechanisms, such as modulation of oncogenes and oncosuppressor genes, cell proliferation, recruitment of undifferentiated stem cells, inflammation, inhibition of intercellular communications, angiogenesis, invasion, and metastasis. The miRNA alterations induced by CS in the lung of mice and rats are similar to those observed in the human respiratory tract. Since a number of miRNAs that are modulated by CS and/or chemopreventive agents are subjected to single nucleotide polymorphisms in humans, they can be evaluated according to toxicogenomic/pharmacogenomics approaches. A variety of cancer chemopreventive agents tested in our laboratory modulated both baseline and CS‐related miRNA and proteome alterations, thus contributing to evaluate both safety and efficacy of dietary and pharmacological agents.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.27814