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Title
Disarming Olig2: Targeting its partner protein Hdac1
Description
Glioblastoma is the most aggressive and lethal brain tumor, due to its resistance to current conventional therapy. The resistance to chemo- and radiotherapy has been attributed to a special population of cells known as glioma stem cells. Previous literature has shown the importance of a Central Nervous System-restricted transcription factor OLIG2 in maintaining the tumor-propagating potential of these glioma stem cells. OLIG2's function was further elucidated, with its pro-mitogenic function due to its ability to negatively regulate the p53 pathway by suppressing the acetylation of the p53 protein's C terminal domain. Past work in our lab has confirmed that one of OLIG2's partner proteins is Histone Deacetylase 1 (HDAC1). In vitro experiments have also shown that targeting HDAC1 using hairpin RNA in glioma stem cells negatively impacts proliferation. In a survival study using a murine glioma model, targeting Hdac1 using hairpin RNA is shown to reduce tumor burden and increase survival. In this paper, we demonstrate that silencing Hdac1 expression reduces proliferation, increases cell death, likely a result of increased acetylation of p53. Olig2 expression levels seem to be unaffected in GSCs, demonstrating that the Hdac1 protein ablation is indeed lethal to GSCs. This work builds upon previously collected results, confirming that Hdac1 is a potential surrogate target for Olig2's pro-mitotic function in regulating the p53 pathway.
Date Created
2017-05
Contributors
- Loo, Vincent You Wei (Author)
- LaBaer, Joshua (Thesis director)
- Mehta, Shwetal (Committee member)
- School of Molecular Sciences (Contributor)
- Barrett, The Honors College (Contributor)
Topical Subject
Resource Type
Extent
21 pages
Language
eng
Copyright Statement
In Copyright
Primary Member of
Series
Academic Year 2016-2017
Handle
https://hdl.handle.net/2286/R.I.43384
Level of coding
minimal
Cataloging Standards
System Created
- 2017-10-30 02:50:58
System Modified
- 2021-08-11 04:09:57
- 3 years 3 months ago
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