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Cofactor of BRCA1 as a modulator of hepatocellular carcinoma growth and migration

Cofactor of BRCA1 (COBRA1) is one of the four subunits that make up the Negative Elongation Factor Complex (NELF) which is involved in the stalling of RNA polymerase II early during transcription elongation. As such, COBRA1 is able to regulate a substantial number of genes involved in a number of pa...

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Main Author: El Zeneini, Eman Mahmoud
Format: Thesis
Published: AUC Knowledge Fountain 2015
Subjects:
Hepatocellular Carcinoma
COBRA1
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access_status_str Open Access
author El Zeneini, Eman Mahmoud
author_browse El Zeneini, Eman Mahmoud
author_facet El Zeneini, Eman Mahmoud
author_sort El Zeneini, Eman Mahmoud
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 Cofactor of BRCA1 (COBRA1) is one of the four subunits that make up the Negative Elongation Factor Complex (NELF) which is involved in the stalling of RNA polymerase II early during transcription elongation. As such, COBRA1 is able to regulate a substantial number of genes involved in a number of pathways, including cell cycle control, metabolism, cell proliferation and DNA repair. In the field of cancer, the role of COBRA1 is not yet fully understood. The aim of our study was to investigate the functional role of COBRA1 in the tumorigenesis of hepatocellular carcinoma (HCC). We investigated the gene expression pattern of COBRA1 in HCC tumors using the publicly available Oncomine Cancer Microarray Database. Results from three different microarray datasets reveal the frequent overexpression of COBRA1 in HCC tumors versus their normal counterparts. To elucidate the biological significance for this overexpression in HCC, RNA interference was used to silence the expression of COBRA1 in the well differentiated HCC cell line, HepG2. The silencing efficiency was confirmed by both reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Interestingly, knockdown of COBRA1 resulted in a significant decrease in cell proliferation, accompanied by a concomitant decrease in the expression of the proliferation marker, Ki-67. A scratch wound healing assay revealed a significant decrease in the migratory potential of the HepG2 cell line in culture upon COBRA1 knockdown. In addition, silencing of COBRA1 was associated with a significant decrease in the expression of survivin, suggesting that survivin might be one of the mechanisms by which COBRA1 mediates its role in the tumorigenicity of HCC. Collectively, data findings presented here highlight an oncogenic role for COBRA1 in hepatocellular carcinoma. To the best of our knowledge, our study provides evidence for the first time to support a positive role for COBRA1 in the growth and migration of HCC.
format Thesis
id oai:fount.aucegypt.edu:etds-1107
institution American University in Cairo (Egypt)
last_indexed 2026-06-10T12:35:39.635Z
license_str Other — see source repository
provenance_str_mv Harvested via OAI-PMH from AUC Knowledge Fountain — bepress
publishDate 2015
publishDateRange 2015
publishDateSort 2015
publisher AUC Knowledge Fountain
publisherStr AUC Knowledge Fountain
record_format dspace
source_str AUC Knowledge Fountain — bepress
spelling oai:fount.aucegypt.edu:etds-1107 Cofactor of BRCA1 as a modulator of hepatocellular carcinoma growth and migration El Zeneini, Eman Mahmoud Cofactor of BRCA1 (COBRA1) is one of the four subunits that make up the Negative Elongation Factor Complex (NELF) which is involved in the stalling of RNA polymerase II early during transcription elongation. As such, COBRA1 is able to regulate a substantial number of genes involved in a number of pathways, including cell cycle control, metabolism, cell proliferation and DNA repair. In the field of cancer, the role of COBRA1 is not yet fully understood. The aim of our study was to investigate the functional role of COBRA1 in the tumorigenesis of hepatocellular carcinoma (HCC). We investigated the gene expression pattern of COBRA1 in HCC tumors using the publicly available Oncomine Cancer Microarray Database. Results from three different microarray datasets reveal the frequent overexpression of COBRA1 in HCC tumors versus their normal counterparts. To elucidate the biological significance for this overexpression in HCC, RNA interference was used to silence the expression of COBRA1 in the well differentiated HCC cell line, HepG2. The silencing efficiency was confirmed by both reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Interestingly, knockdown of COBRA1 resulted in a significant decrease in cell proliferation, accompanied by a concomitant decrease in the expression of the proliferation marker, Ki-67. A scratch wound healing assay revealed a significant decrease in the migratory potential of the HepG2 cell line in culture upon COBRA1 knockdown. In addition, silencing of COBRA1 was associated with a significant decrease in the expression of survivin, suggesting that survivin might be one of the mechanisms by which COBRA1 mediates its role in the tumorigenicity of HCC. Collectively, data findings presented here highlight an oncogenic role for COBRA1 in hepatocellular carcinoma. To the best of our knowledge, our study provides evidence for the first time to support a positive role for COBRA1 in the growth and migration of HCC. 2015-02-01T08:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/108 https://fount.aucegypt.edu/context/etds/article/1107/viewcontent/Thesis_20Final.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 Hepatocellular Carcinoma COBRA1
spellingShingle Hepatocellular Carcinoma
COBRA1
El Zeneini, Eman Mahmoud
Cofactor of BRCA1 as a modulator of hepatocellular carcinoma growth and migration
title Cofactor of BRCA1 as a modulator of hepatocellular carcinoma growth and migration
title_full Cofactor of BRCA1 as a modulator of hepatocellular carcinoma growth and migration
title_fullStr Cofactor of BRCA1 as a modulator of hepatocellular carcinoma growth and migration
title_full_unstemmed Cofactor of BRCA1 as a modulator of hepatocellular carcinoma growth and migration
title_short Cofactor of BRCA1 as a modulator of hepatocellular carcinoma growth and migration
title_sort cofactor of brca1 as a modulator of hepatocellular carcinoma growth and migration
topic Hepatocellular Carcinoma
COBRA1
url https://fount.aucegypt.edu/etds/108
https://fount.aucegypt.edu/context/etds/article/1107/viewcontent/Thesis_20Final.pdf
work_keys_str_mv AT elzeneiniemanmahmoud cofactorofbrca1asamodulatorofhepatocellularcarcinomagrowthandmigration

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