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USP1 targeting impedes GBM growth by inhibiting stem cell maintenance and radioresistance.


ABSTRACT: BACKGROUND:Clinical benefits from standard therapies against glioblastoma (GBM) are limited in part due to intrinsic radio- and chemoresistance of GBM and inefficient targeting of GBM stem-like cells (GSCs). Novel therapeutic approaches that overcome treatment resistance and diminish stem-like properties of GBM are needed. METHODS:We determined the expression levels of ubiquitination-specific proteases (USPs) by transcriptome analysis and found that USP1 is highly expressed in GBM. Using the patient GBM-derived primary tumor cells, we inhibited USP1 by shRNA-mediated knockdown or its specific inhibitor pimozide and evaluated the effects on stem cell marker expression, proliferation, and clonogenic growth of tumor cells. RESULTS:USP1 was highly expressed in gliomas relative to normal brain

SUBMITTER: Lee JK 

PROVIDER: S-EPMC4677407 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature