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Cellular Oncology
Published in: Cellular Oncology 6/2017

01-12-2017 | Original Paper

Opposing roles of the aldo-keto reductases AKR1B1 and AKR1B10 in colorectal cancer

Authors: Betul Taskoparan, Esin Gulce Seza, Secil Demirkol, Sinem Tuncer, Milan Stefek, Ali Osmay Gure, Sreeparna Banerjee

Published in: Cellular Oncology | Issue 6/2017

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Abstract

Purpose

Aldo-keto reductases (including AKR1B1 and AKR1B10) constitute a family of oxidoreductases that have been implicated in the pathophysiology of diabetes and cancer, including colorectal cancer (CRC). Available data indicate that, despite their similarities in structure and enzymatic functions, their roles in CRC may be divergent. Here, we aimed to determine the expression and functional implications of AKR1B1 and AKR1B10 in CRC.

Methods

AKR1B1 and AKR1B10 gene expression levels were analyzed using publicly available microarray data and ex vivo CRC-derived cDNA samples. Gene Set Enrichment Analysis (GSEA), The Cancer Genome Atlas (TCGA) RNA-seq data and The Cancer Proteome Atlas (TCPA) proteome data were analyzed to determine the effect of high and low AKR1B1 and AKR1B10 expression levels in CRC patients. Proliferation, cell cycle progression, cellular motility, adhesion and inflammation were determined in CRC-derived cell lines in which these genes were either exogenously overexpressed or silenced.

Results

We found that the expression of AKR1B1 was unaltered, whereas that of AKR1B10 was decreased in primary CRCs. GSEA revealed that, while high AKR1B1 expression was associated with increased cell cycle progression, cellular motility and inflammation, high AKR1B10 expression was associated with a weak inflammatory phenotype. Functional studies carried out in CRC-derived cell lines confirmed these data. Microarray data analysis indicated that high expression levels of AKR1B1 and AKR1B10 were significantly associated with shorter and longer disease-free survival rates, respectively. A combined gene expression signature of AKR1B10 (low) and AKR1B1 (high) showed a better prognostic stratification of CRC patients independent of confounding factors.

Conclusions

Despite their similarities, the expression levels and functions of AKR1B1 and AKR1B10 are highly divergent in CRC, and they may have prognostic implications.
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Metadata
Title
Opposing roles of the aldo-keto reductases AKR1B1 and AKR1B10 in colorectal cancer
Authors
Betul Taskoparan
Esin Gulce Seza
Secil Demirkol
Sinem Tuncer
Milan Stefek
Ali Osmay Gure
Sreeparna Banerjee
Publication date
01-12-2017
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 6/2017
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-017-0351-7

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