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A role for microRNAs in the etiology...

Avissar-Whiting, Michele.

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A role for microRNAs in the etiology of head and neck squamous cell carcinoma.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	A role for microRNAs in the etiology of head and neck squamous cell carcinoma./
Author:	Avissar-Whiting, Michele.
Description:	148 p.
Notes:	Source: Dissertation Abstracts International, Volume: 71-11, Section: B, page: 6561.
Contained By:	Dissertation Abstracts International71-11B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3430085
ISBN:	9781124304120

A role for microRNAs in the etiology of head and neck squamous cell carcinoma.
Avissar-Whiting, Michele.

A role for microRNAs in the etiology of head and neck squamous cell carcinoma. - 148 p.

Source: Dissertation Abstracts International, Volume: 71-11, Section: B, page: 6561.

Thesis (Ph.D.)--Brown University, 2010.

Head and neck squamous cell carcinomas form a heterogeneous group of cancers of the upper aerodigestive tract, arising from the surface epithelium of the oral cavity, pharynx and larynx. Worldwide, there are about 650,000 new cases annually, which are predominantly associated with behavioral risk factors such as smoking and drinking as well as human papilloma virus infection. Despite advances in multimodality therapy of HNSCC, survival has remained among the worst of the major cancer types. This thesis aimed to determine the role of microRNAs (miRNAs), endogenous small non-coding RNAs, in HNSCC carcinogenesis. MiRNA profiles were determined using a microarray in primary human HNSCC samples compared to non-diseased head and neck epithelial tissues. MiRNA identified as significantly differentially expressed from these profiles were then examined for their ability to distinguish HNSCC from normal epithelia. The associations between the expression of these specific miRNA and clinical, demographic, and exposure histories were examined in a larger case series study of HNSCC. Four miRNAs were found to be significantly differentially expressed in HNSCC tumors compared to normal epithelium (P < 0.0001). A miRNA ratio based on miR-221:miR-375 expression was found to distinguish disease from normal tissue with high specificity and sensitivity (0.93 and 0.92, respectively). Expression of miR-375 was found to increase significantly with increased exposure to alcohol and was differentially expressed in tumors of laryngeal vs oral and pharyngeal origin. Additionally, high miR-21 expression was found to associate significantly with poor survival in HNSCC patients. To better understand the mechanism by which these miRNA elicit their observed effects on this disease we examined potential in-vitro techniques for miRNA overexpression, which suggested that transfection with synthetic mature miRNA mimics may not be an appropriate analog for upregulation of miRNA expression and that vector based systems, which allow for processing by endogenous miRNA machinery may be better suited for functional analysis of miRNA activity. This work has demonstrated that miRNA alterations are important epigenetic determinants of HNSCC carcinogenesis, can be modulated by environmental factors, and ultimately influence the molecular character of the disease.

ISBN: 9781124304120Subjects--Topical Terms:

1017719
Biology, Molecular.

A role for microRNAs in the etiology of head and neck squamous cell carcinoma.
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520 $a Head and neck squamous cell carcinomas form a heterogeneous group of cancers of the upper aerodigestive tract, arising from the surface epithelium of the oral cavity, pharynx and larynx. Worldwide, there are about 650,000 new cases annually, which are predominantly associated with behavioral risk factors such as smoking and drinking as well as human papilloma virus infection. Despite advances in multimodality therapy of HNSCC, survival has remained among the worst of the major cancer types. This thesis aimed to determine the role of microRNAs (miRNAs), endogenous small non-coding RNAs, in HNSCC carcinogenesis. MiRNA profiles were determined using a microarray in primary human HNSCC samples compared to non-diseased head and neck epithelial tissues. MiRNA identified as significantly differentially expressed from these profiles were then examined for their ability to distinguish HNSCC from normal epithelia. The associations between the expression of these specific miRNA and clinical, demographic, and exposure histories were examined in a larger case series study of HNSCC. Four miRNAs were found to be significantly differentially expressed in HNSCC tumors compared to normal epithelium (P < 0.0001). A miRNA ratio based on miR-221:miR-375 expression was found to distinguish disease from normal tissue with high specificity and sensitivity (0.93 and 0.92, respectively). Expression of miR-375 was found to increase significantly with increased exposure to alcohol and was differentially expressed in tumors of laryngeal vs oral and pharyngeal origin. Additionally, high miR-21 expression was found to associate significantly with poor survival in HNSCC patients. To better understand the mechanism by which these miRNA elicit their observed effects on this disease we examined potential in-vitro techniques for miRNA overexpression, which suggested that transfection with synthetic mature miRNA mimics may not be an appropriate analog for upregulation of miRNA expression and that vector based systems, which allow for processing by endogenous miRNA machinery may be better suited for functional analysis of miRNA activity. This work has demonstrated that miRNA alterations are important epigenetic determinants of HNSCC carcinogenesis, can be modulated by environmental factors, and ultimately influence the molecular character of the disease.
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