Page 107 - GPD-4-2

Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
Differences in the expression of genes used

in circadian rhythm generation in adult and
pediatric gliomas

†
†
Austin Tyler Vogt , Veda Sanjay Mohite , Christopher Wayne Chandler ,
Sadia Afrin, and Michael Eric Geusz*
Department of Biological Sciences, College of Arts and Sciences, Bowling Green State University,
Bowling Green, Ohio, United States of America

Abstract
Altered circadian rhythms occur in several types of cancer cells. Expression of PER2,
a core component of the circadian oscillator mechanism, and the related PER3 gene
is suppressed in adult glioblastoma (GBM). GBM cell survival depends on the activity
of the core clock gene ARNTL that expresses BMAL1 protein, and pharmacological
manipulations of BMAL1 activity are promising novel anticancer treatments. Because
circadian clock gene activity in pediatric gliomas is poorly understood relative to
† These authors contributed equally adult GBM, we completed a meta-analysis using 19 public transcriptome datasets to
to this work. evaluate expression of core clock genes and selected clock-controlled genes in adult
*Corresponding author: and pediatric GBM as well as medulloblastoma (MB), pilocytic astrocytoma (PA), and
Michael Eric Geusz ependymoma (EP) tumors. Unlike adult GBM, PER2, and PER3 were not significantly
(mgeusz@bgsu.edu) downregulated in pediatric gliomas relative to non-tumor tissue. Adult GBM tissue
Citation: Vogt AT, Mohite VS, displayed elevated expression of core clock gene CRY1 and clock-controlled gene
Chandler CW, Afrin S, Geusz ME. NFIL3, unlike the pediatric GBM and low-grade gliomas. The TIMELESS clock gene
Differences in the expression of
genes used in circadian rhythm was upregulated in all glioma types except PA. The clock gene set was differentially
generation in adult and pediatric expressed across the four standard MB subtypes in pediatric datasets and was
gliomas. Gene Protein Dis. elevated in bulk-tumor measurements and single-cell RNA sequencing results from
2025;4(2):4112.
doi: 10.36922/gpd.4112 the Group 3 and 4 subtypes. Relative to older patients, MB samples from patients
under 10 years of age had six repressed core clock genes. This study found that several
Received: July 1, 2024
types of malignant pediatric brain tumors have predictable expression patterns of
1st revised: July 29, 2024 specific circadian clock genes and may respond to treatments using pharmacological
2nd revised: January 21, 2025 treatments exploiting these features.
Accepted: February 18, 2025
Keywords: Circadian rhythm; Glioma stem cell; Glioblastoma; Medulloblastoma;
Published online: May 19, 2025
Ependymoma; Pilocytic astrocytoma; Transcriptomics
Copyright: © 2025 Author(s).
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution, 1. Introduction
and reproduction in any medium,
provided the original work is Daily rhythms in behavior and physiology are driven by molecular circadian clocks
properly cited. within individual cells that generate self-sustaining circadian rhythms. These cellular
1
Publisher’s Note: AccScience clocks synchronize to each other and the external cycles of light and darkness, food
Publishing remains neutral with availability, social cues, and other daily events acting on the organism. This entrainment
regard to jurisdictional claims in
published maps and institutional process allows the clocks, which have intrinsic periods near 24 h, to set their phase to
affiliations. match predictable daily events, thereby enabling behaviors, metabolism, cell division,

Volume 4 Issue 2 (2025) 1 doi: 10.36922/gpd.4112