科研之友
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摘要
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 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 Rab7expressing 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.
- 出版日期2014-3-1
