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The impact of smoking on human airwa...

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The impact of smoking on human airway epithelial microRNA and mRNA expression.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	The impact of smoking on human airway epithelial microRNA and mRNA expression./
作者:	Sridhar, Sriram.
面頁冊數:	165 p.
附註:	Adviser: Avrum Spira.
Contained By:	Dissertation Abstracts International70-01B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3345589
ISBN:	9781109001761

The impact of smoking on human airway epithelial microRNA and mRNA expression.
Sridhar, Sriram.

The impact of smoking on human airway epithelial microRNA and mRNA expression. - 165 p.

Adviser: Avrum Spira.

Thesis (Ph.D.)--Boston University, 2009.

Cigarette smoking is the leading cause of preventable death in the US, and is a major risk factor for developing lung cancer and emphysema. Prior studies have demonstrated that smoking causes genetic and molecular alterations throughout epithelium lining the respiratory tract. While the gene expression responses to tobacco exposure in bronchial epithelium have been previously characterized, the impact of smoking on nasal and buccal epithelium remains unclear. Additionally, the regulatory mechanisms mediating smoking-related changes in airway gene expression have not been studied.

ISBN: 9781109001761Subjects--Topical Terms:

1017730
Biology, Genetics.

The impact of smoking on human airway epithelial microRNA and mRNA expression.
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520 $a Cigarette smoking is the leading cause of preventable death in the US, and is a major risk factor for developing lung cancer and emphysema. Prior studies have demonstrated that smoking causes genetic and molecular alterations throughout epithelium lining the respiratory tract. While the gene expression responses to tobacco exposure in bronchial epithelium have been previously characterized, the impact of smoking on nasal and buccal epithelium remains unclear. Additionally, the regulatory mechanisms mediating smoking-related changes in airway gene expression have not been studied.
520 $a We first explored relationships in whole-genome gene expression between extrathoracic (buccal and nasal) and intrathoracic (bronchial) epithelium in healthy current and never smokers. We found that bronchial and nasal epithelium from non-smokers was most similar in gene expression when compared to other tissues. A subset of smoking-induced genes from the bronchus is similarly altered in the nasal and buccal mucosa of smokers, suggesting a common airway-wide response to tobacco exposure.
520 $a We next explored the role of microRNAs (miRNAs) in regulating the airway gene-expression responses to smoking. We examined whole-genome miRNA and mRNA expression in bronchial epithelium from current and never smokers, and found a group of miRNAs which was significantly down-regulated in smokers. We further identified a number of mRNAs whose expression level is highly anti-correlated with miRNA expression in vivo, many of which are putative targets of these miRNAs and are affected by smoking. Modulating mir-218 levels (the miRNA most strongly affected by smoking) in vitro was sufficient to alter expression of its targets and recapitulate some of the airway gene-expression response to cigarette smoke. We extended our studies to buccal and nasal epithelium, demonstrating similar changes in mir-218 expression among current smokers.
520 $a Our results suggest that smoking-related gene expression changes in the mouth and nose reflect those occurring in the bronchus. Additionally, we have demonstrated that some of these changes in the airway are modulated by altered miRNA expression. Together, these findings support the application of mRNA and miRNA profiling of airway epithelium to develop non-invasive biomarkers of host response to tobacco exposure as well as to identify smokers at risk for developing tobacco-related lung disease.
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