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Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

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7.3 Tumour Expression Correlation Results<br />

The PRSS12 gene encodes a protease that can activate tissue plasminogen acti-<br />

vator (tPA) [335], an enzyme which is highly expressed by glioma cells and has<br />

been suggested to promote invasion [168]. We observe a slight up-regulation<br />

in the GNS cell lines and primary GBM <strong>of</strong> PRSS12 (Fig 7.4a), and a slight<br />

down-regulation in grade III astrocytomas (Fig 7.4b).<br />

The LYST gene encodes a vesicular transport protein called the "lysosomal<br />

trafficking regulator" that so far has not been implicated in any neoplasia but<br />

is known to be associated with a rare recessive disorder (Chédiak-Higashi syn-<br />

drome) caused by a microtubule polymerisation defect that decreases phago-<br />

cytosis ability [87]. In line with the hypothetical increase <strong>of</strong> cellular activities<br />

and rates, and thus <strong>of</strong> vesicular transport, in GNS cells, we observed LYST to<br />

be up-regulated in GNS cell lines and primary GBM (Fig 7.4a), and slightly<br />

down-regulated in grade III astrocytomas (Fig 7.4b).<br />

Down-regulated in GNS cell lines. The panels c and d <strong>of</strong> figure 7.4 the core<br />

down-regulated genes found through Tag-seq are used to evaluate the compar-<br />

ison <strong>of</strong> the GBM data to the non-neoplastic tissue data (TCGA dataset), and<br />

the comparison <strong>of</strong> the GBM (grade IV) to the grade III astrocytoma (HGG<br />

dataset). In this comparison the genes that were also identified via qRT-PCR<br />

as being differentially expressed between GNS cell lines and NS cell lines, are<br />

highlighted by the blue colour gradient dots. The trends highlighted in figure<br />

7.4 show matching down-regulation for genes NELL2, TUSC3, ST6GALNAC5,<br />

PLCH1, NDN, MAP6 and PTEN in GNS cell lines and primary GBM, and non<br />

matching down-regulation in GNS cell lines and up-regulation in primary GBM<br />

for genes MAF, MYL9, HMGA2, SDC2, SYNM, IRX2, TES and TAGLN.<br />

The MAF gene encodes a transcription factor and oncoprotein that belongs to<br />

the same AP-1 super-family <strong>of</strong> JUN and FOS. MAF has been associated with<br />

multiple myeloma whereby its up-regulation is suggested to enhance myeloma<br />

proliferation and adhesion to the bone marrow [406]. Although not previously<br />

linked to glioma, we find MAF to be down-regulated in GNS cell lines but<br />

slightly up-regulated in primary GBM, perhaps as an indicator <strong>of</strong> its cell type<br />

restricted proliferation enhancing functions (Fig 7.4c). Accordingly, we ob-<br />

served a slight down-regulation <strong>of</strong> MAF in grade III astrocytoma with respect<br />

to primary GBM (Fig 7.4d).<br />

The protein encoded by the MYL9 gene is a myosin light chain that has<br />

previously been associated with the stem cell component <strong>of</strong> lung adenocar-<br />

cinoma [447] and medullary breast cancer [54] in gene expression pr<strong>of</strong>iling<br />

studies. MYL9 has never been implicated in glioma and we observed down-<br />

178

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