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Gene & Protein in Disease Pediatric glioma circadian clock genes

optic nerve that entrain the SCN clock to external cycles gliomas may also be effective against pediatric GBM
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of light and dark. and ependymomas, which displayed suppressed NR1D2.
PER3 is perhaps the most poorly understood gene of Expression of the BHLHE41 (DEC2) gene only showed
the PER family. Of the three PER genes, it appears to have altered expression (upregulation) in pediatric PA and EP
the least importance in the circadian clock mechanism, tumors. The DEC2 protein is a transcription factor that
as shown by behavioral and gene knock-out studies in interacts with BMAL1 and has been examined in cancer
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mice. Nevertheless, its suppression in cancers, including cells along with BHLHE40 (DEC1).
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gliomas, indicates it could have important functions in In this study, we compared clock gene expression in the
processes other than the circadian clock, particularly pediatric and adult PA tumors. Unlike pediatric PA, CRY1
in cancer cells lacking a functional clock. Although and RORA were significantly overexpressed in the adult
important in tumor functioning, the role of the PER genes PA. These genes were repressed in one of the pediatric
in cancer remains unclear. For example, PER3 expression is PA datasets, indicating a distinctly altered pattern that
elevated in U118MG cells derived from an astroblastoma, may reflect different circadian clock functioning. Some
a pediatric and adult glioma, and PER3 overexpression and of these differences could be related to the tumor location
interference showed that migration and invasion abilities or tissue of origin. There are reported differences in the
are positively correlated with PER3 expression. Thus, preferred locations for PA and EP tumors according to
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PER3 may play a role in sustaining the stem cell state in age, with adult PA appearing more often in the cerebrum
tumors. than cerebellum and adult EP frequently appearing in the
spine. Similarly, pediatric and adult medulloblastomas
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However, another study reported that overexpression are reported to differ in their expression of the wingless-
of PER3 caused a loss of cancer stem cell behaviors and type (WNT) and sonic hedgehog (SHH) genes that
marker proteins, including NOTCH and SOX2, in the drive developmental changes and are used to categorize
HCT-116 colorectal cell line. This result is not, however, tumor subtypes. The potential treatment of adult GBM
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contradictory with our findings because the datasets mentioned above that suppresses BMAL1 activity by
we examined used RNA from bulk tumor tissues and elevating CRY protein levels might also be useful in
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would not be expected to reflect GSC gene expression treating SHH-type MB because we found, using the
alone. A particular cell subpopulation that dominates in dataset from Kool et al., that patients under 10 years of
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the whole-tumor RNA examined in these studies would age have significantly repressed CRY2 expression relative
be more highly represented in the results. An analysis of to older patients.
PER3 specifically in GSCs is needed to resolve the role
of this regulator in GSCs. Furthermore, these results do The differences in clock gene expression between the
not take into consideration the different states of GSCs, pediatric and adult gliomas could result from the very
including variations between GSC classes. Furthermore, different growth and neurogenesis conditions occurring
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the different GBM tumor subclasses were not considered, in these two nervous systems. The transcription factor
except for the pHGG scSCN-seq study that identified a and stem cell marker SOX2 upregulates circadian clock
mesenchymal cell type. The mesenchymal tumor subclass genes, producing higher amplitude circadian rhythms in
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is particularly enriched in GSCs. 91 PER gene expression in the SCN. It may serve the same
function in circadian clocks of cancer cells, particularly in
4.2.3. Age-dependent expression differences of other GSCs, where elevated SOX2 protein is a known marker. We
clock genes speculate that SOX2 or related morphogenic genes induced
Considering the other observed differences between in the developing brain maintains PER gene expression in
pediatric and adult glioma, the lack of elevated CRY1 pediatric gliomas.
expression in pediatric GBM and LG bulk tumors suggests Recurrent tumors are frequently enriched with stem
a possible path for controlling pediatric tumors that has cell markers, which supports their often more aggressive
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not been explored. NR1D2 was often repressed in the nature. GSCs in vitro display circadian rhythms and
GBM datasets but not as extensively in the LG pediatric elevated expression of some core clock genes such as
and adult PA tumors, suggesting that treatment strategies ARNTL. Nevertheless, the pediatric EP and GBM datasets
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may need to be adjusted according to tumor type. These examined here only showed elevated expression of DBP in
results were not consistent with reported overexpression in the recurrent tumors, and in only one EP dataset. Although
adult GBM cells that also promotes cell proliferation and few differences between recurrent and original tumors
migration. Nevertheless, Rev-erb-alpha and Rev-erb- were observed, this does suggest that any pharmacological
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beta agonists SR9009 and SR9011, which suppress adult tools targeting clock genes may be equally useful for

Volume 4 Issue 2 (2025) 16 doi: 10.36922/gpd.4112