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- W2102039405 abstract "Abstract Great interest persists in useful prognostic and therapeutic targets in glioblastoma. In this study, we report the definition of miRNA (miR)-148a as a novel prognostic oncomiR in glioblastoma. miR-148a expression was elevated in human glioblastoma specimens, cell lines, and stem cells (GSC) compared with normal human brain and astrocytes. High levels were a risk indicator for glioblastoma patient survival. Functionally, miR-148a expression increased cell growth, survival, migration, and invasion in glioblastoma cells and GSCs and promoted GSC neurosphere formation. Two direct targets of miR-148a were identified, the EGF receptor (EGFR) regulator MIG6 and the apoptosis regulator BIM, which rescue experiments showed were essential to mediate the oncogenic activity of miR-148a. By inhibiting MIG6 expression, miR-148a reduced EGFR trafficking to Rab7-expressing compartments, which includes late endosomes and lysosomes. This process coincided with reduced degradation and elevated expression and activation of EGFR. Finally, inhibition of miR-148a strongly suppressed GSC and glioblastoma xenograft growth in vivo. Taken together, our findings provide a comprehensive analysis of the prognostic value and oncogenic function of miR-148a in glioblastoma, further defining it as a potential target for glioblastoma therapy. Cancer Res; 74(5); 1541–53. ©2014 AACR." @default.
- W2102039405 created "2016-06-24" @default.
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- W2102039405 date "2014-03-01" @default.
- W2102039405 modified "2023-10-12" @default.
- W2102039405 title "microRNA-148a Is a Prognostic oncomiR That Targets MIG6 and BIM to Regulate EGFR and Apoptosis in Glioblastoma" @default.
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- W2102039405 doi "https://doi.org/10.1158/0008-5472.can-13-1449" @default.
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