Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

6.7 Isoform Differential Expression Results
miR-34a transfected cells generated xenografts that were statistically
significantly smaller than control miR transfected xenografts, demon-
strating that miR-34a expression inhibits in vivo glioblastoma xenograft
growth [278]. In our microRNA prediction analysis miR-34a is predicted
to target C1orf9, an open reading frame 9 of chromosome 1 since no p53
targeting is predicted due to the deletion of the p53 genomic location
within the GNS cell lines.
· miR-26a is up-regulated in glioblastoma and targets PTEN through the
direct binding in its 3'UTR of the B2 and B3 sites, mediating transla-
tional repression and reduced steady-state levels of the protein. West-
ern blotting demonstrated that miR-26a over-expression achieved a 50%
knockdown of PTEN protein in two glioblastoma cell lines, accompa-
nied by an enhanced Akt signaling pathway. In our microRNA mi-
croarray dataset we observe up-regulation of miR-26a as well. In addi-
tion to enhancing tumourigenesis, miR-26a effectively represses endoge-
nous PTEN protein in a relevant PDGF-driven glioma model system.
The miR-26a-mediated knockdown of EZH2, a histone methylatrans-
ferase, and SMAD1, a transcription factor, was also observed in glioblas-
toma [259,364]. In our analysis miR-26a was predicted to target the
SMAD1 gene, of which two isoforms were detected through tag mapping
(Fig 6.20).
· miR-10b is up-regulated in glioblastomas but its function has not been
described yet. Increased levels of miR-10b in breast cancer correlated
with the disease’s progression [259,364]. In our microRNA microarray
dataset miR-10b is also up-regulated.
· miR-451 inhibited the growth of transfected glioblastoma cells, as de-
tected by neurosphere formation assays [259,364]. We found miR-451 to
be up-regulated in our microRNA microarray dataset, in line with its
role as a cell cycle breaker and growth inhibitor.
· miR-129-3p is found to be down-regulated in glioblastomas but its func-
tion remains unknown to date [259,364]. Interestingly, we observed miR-
129-3p to be up-regulated in our microRNA microarray dataset, possibly
indicating a different regulation in action at the stem cell level.
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