PLEK2, RRM2, GCSH: A Novel WWOX-Dependent Biomarker Triad of Glioblastoma at the Crossroads of Cytoskeleton Reorganization and Metabolism Alterations

Glioblastoma is one of the deadliest human cancers. Its malignancy depends on cytoskeleton reorganization, which is related to, e.g., epithelial-to-mesenchymal transition and metastasis. The malignant phenotype of glioblastoma is also affected by the WWOX gene, which is lost in nearly a quarter of g...

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Bibliographic Details
Published in:Cancers 2021-06, Vol.13 (12), p.2955
Main Authors: Kałuzińska, Żaneta, Kołat, Damian, Bednarek, Andrzej K., Płuciennik, Elżbieta
Format: Article
Language:English
Subjects:
Alzheimer's disease
Bioinformatics
Biomarkers
Brain cancer
Brain research
Cell cycle
Cytoskeleton
DNA microarrays
Genes
Genotype & phenotype
Glioblastoma
HOXA1 protein
Kinases
Learning algorithms
Machine learning
Malignancy
Mesenchyme
Metabolism
Metastases
Neural stem cells
Phenotypes
Progenitor cells
Therapeutic targets
Tumor suppressor genes
Tumors
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Summary:Glioblastoma is one of the deadliest human cancers. Its malignancy depends on cytoskeleton reorganization, which is related to, e.g., epithelial-to-mesenchymal transition and metastasis. The malignant phenotype of glioblastoma is also affected by the WWOX gene, which is lost in nearly a quarter of gliomas. Although the role of WWOX in the cytoskeleton rearrangement has been found in neural progenitor cells, its function as a modulator of cytoskeleton in gliomas was not investigated. Therefore, this study aimed to investigate the role of WWOX and its collaborators in cytoskeleton dynamics of glioblastoma. Methodology on RNA-seq data integrated the use of databases, bioinformatics tools, web-based platforms, and machine learning algorithm, and the obtained results were validated through microarray data. PLEK2, RRM2, and GCSH were the most relevant WWOX-dependent genes that could serve as novel biomarkers. Other genes important in the context of cytoskeleton (BMP4, CCL11, CUX2, DUSP7, FAM92B, GRIN2B, HOXA1, HOXA10, KIF20A, NF2, SPOCK1, TTR, UHRF1, and WT1), metabolism (MTHFD2), or correlation with WWOX (COL3A1, KIF20A, RNF141, and RXRG) were also discovered. For the first time, we propose that changes in WWOX expression dictate a myriad of alterations that affect both glioblastoma cytoskeleton and metabolism, rendering new therapeutic possibilities.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13122955