Abstract
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. What's new? Evidence suggests that immune cells can contribute to the outcome of chemotherapy. Conversely, some anti-tumor drugs affect the activity of immune cells such as dendritic cells (DCs), which play a crucial role in the immune response against tumors. In this study, the authors found that doxorubicin and vinblastine impair the immune-stimulating activity of a subclass of human DCs, while methotrexate, mitomycin C, and paclitaxel had no effect. These results may have implications for the design of treatment modalities for tumor patients that combine immunotherapeutic strategies and chemotherapy.
| Original language | English |
|---|---|
| Pages (from-to) | 2763-2773 |
| Number of pages | 11 |
| Journal | International Journal of Cancer |
| Volume | 131 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 15 2012 |
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Keywords
- chemopreventive agents
- cigarette smoke
- microRNAs
- proteome
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Smoke-induced microRNA and related proteome alterations. Modulation by chemopreventive agents. / De Flora, Silvio; Balansky, Roumen; D'Agostini, Francesco; Cartiglia, Cristina; Longobardi, Mariagrazia; Steele, Vernon E.; Izzotti, Alberto.
In: International Journal of Cancer, Vol. 131, No. 12, 15.12.2012, p. 2763-2773.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Smoke-induced microRNA and related proteome alterations. Modulation by chemopreventive agents
AU - De Flora, Silvio
AU - Balansky, Roumen
AU - D'Agostini, Francesco
AU - Cartiglia, Cristina
AU - Longobardi, Mariagrazia
AU - Steele, Vernon E.
AU - Izzotti, Alberto
PY - 2012/12/15
Y1 - 2012/12/15
N2 - 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. What's new? Evidence suggests that immune cells can contribute to the outcome of chemotherapy. Conversely, some anti-tumor drugs affect the activity of immune cells such as dendritic cells (DCs), which play a crucial role in the immune response against tumors. In this study, the authors found that doxorubicin and vinblastine impair the immune-stimulating activity of a subclass of human DCs, while methotrexate, mitomycin C, and paclitaxel had no effect. These results may have implications for the design of treatment modalities for tumor patients that combine immunotherapeutic strategies and chemotherapy.
AB - 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. What's new? Evidence suggests that immune cells can contribute to the outcome of chemotherapy. Conversely, some anti-tumor drugs affect the activity of immune cells such as dendritic cells (DCs), which play a crucial role in the immune response against tumors. In this study, the authors found that doxorubicin and vinblastine impair the immune-stimulating activity of a subclass of human DCs, while methotrexate, mitomycin C, and paclitaxel had no effect. These results may have implications for the design of treatment modalities for tumor patients that combine immunotherapeutic strategies and chemotherapy.
KW - chemopreventive agents
KW - cigarette smoke
KW - microRNAs
KW - proteome
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U2 - 10.1002/ijc.27814
DO - 10.1002/ijc.27814
M3 - Article
VL - 131
SP - 2763
EP - 2773
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 12
ER -