GAPDH: A common housekeeping gene with an oncogenic role in pan-cancer
Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is one of the most prominent housekeeping proteins and is widely used as an internal control in some semi-quantitative assays. In addition to glycolysis, GAPDH is involved in several cancer-related biological processes and has been reported to be comm...
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Published in | Computational and structural biotechnology journal Vol. 21; pp. 4056 - 4069 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Research Network of Computational and Structural Biotechnology
01.01.2023
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is one of the most prominent housekeeping proteins and is widely used as an internal control in some semi-quantitative assays. In addition to glycolysis, GAPDH is involved in several cancer-related biological processes and has been reported to be commonly dysregulated in multiple cancer types. Therefore, its role in the physiological process of cancer needs to be urgently elucidated. Pan-cancer analysis indicated that
GAPDH
is ubiquitously highly expressed in most cancer types, and that patients with a high
GAPDH
expression of in tumor tissues have a poor prognosis. The concordance of
GAPDH
expression in tumors with the infiltration of immune cells and immune checkpoints implies a certain association between GAPDH and the tumor microenvironment as well as tumor development. Gene Set Enrichment Analysis revealed that
GAPDH
may contribute to multiple important cancer-related pathways and biological processes. Multi-omics analysis and
in vitro
cell experiments revealed that
GAPDH
overexpression is regulated by DNA copy number amplification and promoter methylation modification. Importantly, a transcription factor, forkhead box M1 (FOXM1), which is capable of regulating GAPDH expression, was also identified and was confirmed to be an oncogene and ubiquitously highly expressed in multiple cancer types. Semi-quantitative chromatin immunoprecipitation, quantitative PCR, and dual-luciferase assays showed that FOXM1 mainly binds to the promoter region of
GAPDH
in two cancer cell lines. The present findings revealed the implication of GAPDH in tumor development, thus bringing attention to this important molecule and casting doubts on its role as an internal reference gene in cancer studies.
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GAPDH was ubiquitously overexpressed in most cancer types.
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GAPDH overexpression is associated with poor prognosis.
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GAPDH correlated with immune cells infiltration and immune checkpoint gene expression.
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GAPDH is regulated by DNA copy number, methylation and the transcription factor FOXM1. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2001-0370 2001-0370 |
DOI: | 10.1016/j.csbj.2023.07.034 |