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• W2396892013 abstract "Deregulation of microRNA expression is common in a variety of malignancies, including glioma. Several studies have demonstrated the role of miRNAs in regulating glioma stem cell (GSC) properties. In addition, DICER, which regulates the processing of precursor miRNAs to the mature double-stranded form, is down-regulated in multiple forms of cancer. To determine the role of DICER and miRNA regulation in the development and progression of glioblastoma, we investigated the link between miRNA deregulation and GSC characteristics. Our in vitro studies using GSC 7-2 and U251 glioma cell line demonstrated that decreased DICER expression by shRNA treatment results in a global decrease in expression of miRNAs, the majority of which are tumor suppressor miRNAs such as the let-7 family of miRNAs. DICER knockdown increased proliferation of GSCs, while their “stemness” properties, such as their ability to form neurospheres and the levels of stem cell markers such as Sox2 and Bmi1, decreased upon shDicer treatment. Intracranial injection of GSC 7-2 and U251 cells treated with shDicer resulted in decreased overall survival in xenografted mice. Further analysis of the tumors isolated from these mice demonstrated that DICER knockdown results in a relative increase in tumor cell proliferation, as shown by increased ki-67 labeling (30% Ki67 positive nuclei in shDicer versus 15% in shControl tumors), a decrease in expression of Sox2 (stemness marker; 13% in shDicer versus 31% in shControl tumors), and increase in expression of GFAP (astrocytic differentiation marker). Analysis of data from the Cancer Genome Atlas (TCGA) database suggests that high Dicer expression level is correlated with better prognosis of GBM patients and this supports our in vivo data. Our results highlight the role of DICER and miRNAs as potential regulators of GSC proliferation, stem- versus progenitor-like state, and their potential link to development or progression of glioma tumors." @default.
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• W2396892013 date "2015-11-01" @default.
• W2396892013 modified "2023-09-23" @default.
• W2396892013 title "CBIO-22DICER AND miRNAs REGULATE GLIOMA STEM CELL CHARACTERISTICS" @default.
• W2396892013 doi "https://doi.org/10.1093/neuonc/nov209.22" @default.
• W2396892013 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4638664" @default.
• W2396892013 hasPublicationYear "2015" @default.
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