Abstract

Abstract Introduction: Glioblastoma (GBM) is the most lethal primary brain tumor. The GBM stem cells are treatment-resistant cells. We performed an RNAi screen to identify genetic drivers of the GSC state. LIN9 suppression scored strongly in the opposite direction: LIN9 suppression led to a significant increase in neurosphere size and number. In other cellular contexts, LIN9 interacts with pRB and cooperates to promote differentiation. It also inhibits DNA synthesis and oncogenic transformation. The purpose of this study is to better understand the role of LIN9 in GBM. Methods: Lentivirus for suppression and overexpression of LIN9 was produced via transfection of 293T cells. We transduced patient-derived 0308 GSCs. qRT-PCR was used to determine the expression of various genes. Results: LIN9 suppression in 0308 GSCs results in increased sphere formation and increased cell proliferation but not increased cell size. Additionally, LIN9 suppression results in upregulation of Sox2 in human astrocytes. In contrast, LIN9 overexpression in 0308 cells results in decreased sphere formation and decreased proliferation. Further ongoing experiments will determine if suppression and overexpression of LIN9 have an effect on the expression of stem cell markers (ex. SOX2, Nestin, OLIG2) and differentiation markers (ex. GFAP, MAPK2, GAL4). We expect LIN9 suppression will result in an increase in the expression of stem cell markers and a decrease in expression of differentiation markers. We also expect the opposite results for LIN9 overexpression. Conclusions: LIN9 is a potentially important negative regulator of the glioblastoma stem cell state. Citation Format: Farid Farkouh, Milan G. Chheda, Arijita Jash. LIN9 as a potential negative regulator of the glioblastoma stem cell state [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5300.

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