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Mechanism of NANOGP8 in Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is an incurable brain tumor, with patients only expecting to live 15 to 16 months post-diagnosis with the most current treatments options including surgery, chemotherapy, and radiation. How GBM resist treatment is still not very well known. However, cancer stem cells (CSCs), a subset of cells in GBM tissue considered responsible for therapeutic resistance and the poor patient prognosis. NANOG, a homeobox gene, is responsible for maintaining pluripotency of embryonic stem cells and is observed in CSCs. NANOGP8, a retrogene in the NANOG family is expressed in CSCs and provides cells with stem-like characteristics previously observed in stem cells. Thus, we hypothesize that NANOGP8 is not only useful as diagnostic and/or prognostic marker, but a target to improve the efficacy of current GBM treatments since it regulates signaling pathways responsible for cell proliferation. I will investigate the mechanisms in which NANOGP8 expression starts in CSCs and increase TMZ efficacy by silencing embryonic stem cell genes in Glioblastoma. As a retrogene, NANOGP8 derive from reverse transcription of the parent gene NANOG and lacks the promoters for expression in cells. We expect to detect some modifications to the upstream sequence of NANOGP8 that may serve as initiators of expression, such as an insertion of a promotor. Although NANOGP8 has similar function to original NANOG parent gene, NANOGP8 may also have additional oncogenic functions making CSCs more resistant to therapy.

Identiferoai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:etd-7853
Date01 January 2019
CreatorsSmith, Jonhoi
PublisherSTARS
Source SetsUniversity of Central Florida
LanguageEnglish
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceElectronic Theses and Dissertations

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