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Transcriptional regulatory networks in Hepatitis C virus_induced hepatocellular carcinoma

HCV is an epidemic affecting an estimated 160 million individuals worldwide or approximately 2.35% of the world’s population.(1) This is partly because HCV exhibits high genetic variation which thereby characterizes each region with its own genetic prevalence. Therefore, understanding the transcript...

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Main Author: Zahra, Marwa
Format: Thesis
Published: AUC Knowledge Fountain 2015
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access_status_str Open Access
author Zahra, Marwa
author_browse Zahra, Marwa
author_facet Zahra, Marwa
author_sort Zahra, Marwa
collection Thesis
dc_rights_str_mv The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy.
description HCV is an epidemic affecting an estimated 160 million individuals worldwide or approximately 2.35% of the world’s population.(1) This is partly because HCV exhibits high genetic variation which thereby characterizes each region with its own genetic prevalence. Therefore, understanding the transcriptional regulatory elements that influence the progression of liver disease in the presence of HCV infection is thereby crucial for diagnostic and therapeutic purposes. Systems biology provides a road map by which these elements may be easily identified. In this study 124 microarray samples were assessed in order to determine differentially expressed genes for 4 tissue types/conditions (normal, cirrhosis, cirrhosis HCC, and HCC). Differentially expressed genes were assessed for their functional clustering and those genes were annotated with their potential transcription factors and miRNAs. Transcriptional regulatory networks were constructed to visualize each pairwise comparison between the 4 tissue types/conditions. In this study that 12 transcription factors were found to have high expression patterns amongst all 6 pairwise comparisons and these transcription factors also provide insight the conditions of the liver as it progresses through hepatic cirrhosis, hepatic steatosis, and the induction of cancer. With the plethora of miRNAs that are found in the liver, each liver condition was found to have its own signature miRNA expression pattern. In the 6 pairwise comparisons 14 miRNAs were found to have high expression patterns in all 6 pairwise comparisons and their regulation in HCC was determined as well as their impact on cellular homeostasis. Based on the findings of this study and a systematic analysis of many studies it can be concluded that as the liver progresses from cirrhosis to steatosis and eventually becoming carcinomic there are specific transcription factors regulating this transition through each stage. Whereas the condition of the liver digresses, the down-regulation of miRNAs’ expression makes the transition of the liver through each pathological stage more apparent. Therefore, an understanding of the transcriptional regulatory attributes acts as a road map to provide interference strategies in order to target the stages in the progression of HCV induced HCC.
format Thesis
id oai:fount.aucegypt.edu:etds-1384
institution American University in Cairo (Egypt)
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license_str Other — see source repository
provenance_str_mv Harvested via OAI-PMH from AUC Knowledge Fountain — bepress
publishDate 2015
publishDateRange 2015
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publisher AUC Knowledge Fountain
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spelling oai:fount.aucegypt.edu:etds-1384 Transcriptional regulatory networks in Hepatitis C virus_induced hepatocellular carcinoma Zahra, Marwa HCV is an epidemic affecting an estimated 160 million individuals worldwide or approximately 2.35% of the world’s population.(1) This is partly because HCV exhibits high genetic variation which thereby characterizes each region with its own genetic prevalence. Therefore, understanding the transcriptional regulatory elements that influence the progression of liver disease in the presence of HCV infection is thereby crucial for diagnostic and therapeutic purposes. Systems biology provides a road map by which these elements may be easily identified. In this study 124 microarray samples were assessed in order to determine differentially expressed genes for 4 tissue types/conditions (normal, cirrhosis, cirrhosis HCC, and HCC). Differentially expressed genes were assessed for their functional clustering and those genes were annotated with their potential transcription factors and miRNAs. Transcriptional regulatory networks were constructed to visualize each pairwise comparison between the 4 tissue types/conditions. In this study that 12 transcription factors were found to have high expression patterns amongst all 6 pairwise comparisons and these transcription factors also provide insight the conditions of the liver as it progresses through hepatic cirrhosis, hepatic steatosis, and the induction of cancer. With the plethora of miRNAs that are found in the liver, each liver condition was found to have its own signature miRNA expression pattern. In the 6 pairwise comparisons 14 miRNAs were found to have high expression patterns in all 6 pairwise comparisons and their regulation in HCC was determined as well as their impact on cellular homeostasis. Based on the findings of this study and a systematic analysis of many studies it can be concluded that as the liver progresses from cirrhosis to steatosis and eventually becoming carcinomic there are specific transcription factors regulating this transition through each stage. Whereas the condition of the liver digresses, the down-regulation of miRNAs’ expression makes the transition of the liver through each pathological stage more apparent. Therefore, an understanding of the transcriptional regulatory attributes acts as a road map to provide interference strategies in order to target the stages in the progression of HCV induced HCC. 2015-06-01T07:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/385 https://fount.aucegypt.edu/context/etds/article/1384/viewcontent/Vancouver_20thesis_20paper.pdf The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. Theses and Dissertations AUC Knowledge Fountain HCV HCC
spellingShingle HCV
HCC
Zahra, Marwa
Transcriptional regulatory networks in Hepatitis C virus_induced hepatocellular carcinoma
title Transcriptional regulatory networks in Hepatitis C virus_induced hepatocellular carcinoma
title_full Transcriptional regulatory networks in Hepatitis C virus_induced hepatocellular carcinoma
title_fullStr Transcriptional regulatory networks in Hepatitis C virus_induced hepatocellular carcinoma
title_full_unstemmed Transcriptional regulatory networks in Hepatitis C virus_induced hepatocellular carcinoma
title_short Transcriptional regulatory networks in Hepatitis C virus_induced hepatocellular carcinoma
title_sort transcriptional regulatory networks in hepatitis c virus induced hepatocellular carcinoma
topic HCV
HCC
url https://fount.aucegypt.edu/etds/385
https://fount.aucegypt.edu/context/etds/article/1384/viewcontent/Vancouver_20thesis_20paper.pdf
work_keys_str_mv AT zahramarwa transcriptionalregulatorynetworksinhepatitiscvirusinducedhepatocellularcarcinoma