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Open AccessArticle

Weighted Correlation Network Analysis Reveals CDK2 as a Regulator of a Ubiquitous Environmental Toxin-Induced Cell-Cycle Arrest

Julius-Bernstein-Institute for Physiology, Martin-Luther-University Halle-Wittenberg, 06112 Halle (Saale), Germany
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Cells 2020, 9(1), 143; https://doi.org/10.3390/cells9010143
Received: 9 December 2019 / Revised: 20 December 2019 / Accepted: 23 December 2019 / Published: 7 January 2020
(This article belongs to the Section Cell Signaling and Regulated Cell Death)
Environmental food contaminants constitute a threat to human health. For instance, the globally spread mycotoxin Ochratoxin A (OTA) contributes to chronic kidney damage by affecting proximal tubule cells via unknown mechanisms. We applied a top-down approach to identify relevant toxicological mechanisms of OTA using RNA-sequencing followed by in-depth bioinformatics analysis and experimental validation. Differential expression analyses revealed that OTA led to the regulation of gene expression in kidney human cell lines, including for genes enriched in cell cycle-related pathways, and OTA-induced gap 1 and 2 (G1 and G2) cell-cycle arrests were observed. Weighted correlation network analysis highlighted cyclin dependent kinase 2 (CDK2) as a putative key regulator of this effect. CDK2 was downregulated by OTA exposure, and its overexpression partially blocked the OTA-induced G1 but not G2 cell-cycle arrest. We, therefore, propose CDK2 as one of the key regulators of the G1 cell-cycle arrest induced by low nanomolar concentrations of OTA.
Keywords: transcriptomics; human kidney; nephrotoxicity; ochratoxin A; WGCNA; cell cycle; CDK2; CDKN1A/p21 transcriptomics; human kidney; nephrotoxicity; ochratoxin A; WGCNA; cell cycle; CDK2; CDKN1A/p21
MDPI and ACS Style

Dubourg, V.; Nolze, A.; Kopf, M.; Gekle, M.; Schwerdt, G. Weighted Correlation Network Analysis Reveals CDK2 as a Regulator of a Ubiquitous Environmental Toxin-Induced Cell-Cycle Arrest. Cells 2020, 9, 143.

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