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dc.contributor.advisor Amleh, Asma Abd Elhamied, Noha Saad 2018-05-15T07:21:55Z 2020-05-14T22:00:07Z Spring 2018 en_US 2018-05-15
dc.description.abstract Being one of the four subunits that makes up the Negative Elongation Factor Complex (NELF), Cofactor of BRCA1 (COBRA1); also known as NELF-B, is able to regulate a number of genes involved in cellular proliferation, metabolism, cell cycle progression and DNA repair. In addition, COBRA1 was shown to interact with other transcription factors such as BRCA1, AP-1 complex and several nuclear receptors. Despite the evidences that suggest COBRA1 as a potential player involved in the progression of a number of cancers, its role in cervical cancer has not been previously investigated. To date, it has been studied in breast, upper gastrointestinal and liver cancers. The main objective of our study was to investigate the potential involvement of COBRA1 in cervical cancer progression. We first did in-silico analysis of the expression patterns of COBRA1 in cervical cancer tissues relative to normal cervical tissues using the publicly available Oncomine Cancer Microarray Database. Search results revealed a significant upregulation of COBRA1 in two mRNA microarray datasets. RNA interference technique was then used to knockdown COBRA1 expression in cervical cancer cell line, HeLa. Once a successful siRNA mediated silencing at the RNA and protein levels of COBRA1 was established and confirmed through semi-quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western Blot, we investigated its consequences on proliferation, migration and survival of HeLa cells. Interestingly, COBRA1 depletion resulted in a significant increase in the mRNA expression of Trefoil Factor 1 (TFF1) accompanied by a subsequent decrease in the β-catenin mRNA levels. These findings suggests an effect for COBRA1 on the Wnt/β-catenin signalling pathway, which could be mediated through TFF1. In addition, COBRA1 silencing resulted in significant decrease in the expression of survivin 2B and survivin DeltaEX3 isoforms while the observed decrease in survivin wild type form was found to be statistically insignificant. Survivin is known to play a major role in cancer cells proliferation and survival. Yet, the finding that the noted decrease in β-catenin and survivin expression was not reflected on the proliferation and migration abilities of HeLa is not conclusive and requires further investigations. Taken together, these findings could help as an initial step in identifying the role of COBRA1 in cervical cancer tumorigenesis. en_US
dc.description.sponsorship I am sincerely thankful to Mr. Moataz Al-Alfi for partially funding my studies at the AUC. I would to express much gratitude to the AUC for the research grant that supported this work. en_US
dc.format.extent 55 p. en_US
dc.format.medium theses en_US
dc.language.iso en en_US
dc.rights Author retains all rights with regard to copyright. en
dc.subject COBRA1 en_US
dc.subject Cervical cancer en_US
dc.subject HeLa en_US
dc.subject.lcsh Thesis (M.S.)--American University in Cairo en_US
dc.title HeLa cell line, a model to study the role of cofactor of BRCA1 in cervical cancer en_US
dc.type Text en_US
dc.subject.discipline Biotechnology en_US
dc.rights.access This item is restricted for 2 years from the date issued en_US
dc.contributor.department American University in Cairo. Dept. of Biology en_US
dc.description.irb American University in Cairo Institutional Review Board approval is not necessary for this item, since the research is not concerned with living human beings or bodily tissue samples. en_US
dc.contributor.committeeMember Amleh, Asma
dc.contributor.committeeMember Abdelnaser, Anwar
dc.contributor.committeeMember Abou Aisha, Khaled
dc.contributor.committeeMember Mamdouh, Wael

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  • Theses and Dissertations [1841]
    This collection includes theses and dissertations authored by American University in Cairo graduate students.

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