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Open AccessFeature PaperArticle

Analysis of the Circadian Regulation of Cancer Hallmarks by a Cross-Platform Study of Colorectal Cancer Time-Series Data Reveals an Association with Genes Involved in Huntington’s Disease

by Müge Yalçin 1,2,†, Rukeia El-Athman 1,2,†, Koliane Ouk 3,4, Josef Priller 3,4,5 and Angela Relógio 1,2,6,*
1
Institute for Theoretical Biology (ITB), Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
2
Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumour Immunology, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
3
Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
4
German Center for Neurodegenerative Diseases (DZNE), 10117 Berlin, Germany
5
Dementia Research Institute (DRI), University of Edinburgh and UK DRI, Edinburgh EH16 4SB, UK
6
Department of Human Medicine, Institute of Systems Medicine and Bioinformatics, MSH Medical School Hamburg—University of Applied Sciences and Medical University, 20457 Hamburg, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally for the work.
Cancers 2020, 12(4), 963; https://doi.org/10.3390/cancers12040963
Received: 4 March 2020 / Revised: 7 April 2020 / Accepted: 10 April 2020 / Published: 13 April 2020
(This article belongs to the Special Issue Applied Genomics and Cancer Therapeutics)
Accumulating evidence points to a link between circadian clock dysfunction and the molecular events that drive tumorigenesis. Here, we investigated the connection between the circadian clock and the hallmarks of cancer in an in vitro model of colorectal cancer (CRC). We used a cross-platform data normalization method to concatenate and compare available microarray and RNA-sequencing time series data of CRC cell lines derived from the same patient at different disease stages. Our data analysis suggests differential regulation of molecular pathways between the CRC cells and identifies several of the circadian and likely clock-controlled genes (CCGs) as cancer hallmarks and circadian drug targets. Notably, we found links of the CCGs to Huntington’s disease (HD) in the metastasis-derived cells. We then investigated the impact of perturbations of our candidate genes in a cohort of 439 patients with colon adenocarcinoma retrieved from the Cancer Genome Atlas (TCGA). The analysis revealed a correlation of the differential expression levels of the candidate genes with the survival of patients. Thus, our study provides a bioinformatics workflow that allows for a comprehensive analysis of circadian properties at different stages of colorectal cancer, and identifies a new association between cancer and HD. View Full-Text
Keywords: circadian clock; colorectal cancer; drug targets; high-throughput time course data; Huntington’s disease circadian clock; colorectal cancer; drug targets; high-throughput time course data; Huntington’s disease
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Yalçin, M.; El-Athman, R.; Ouk, K.; Priller, J.; Relógio, A. Analysis of the Circadian Regulation of Cancer Hallmarks by a Cross-Platform Study of Colorectal Cancer Time-Series Data Reveals an Association with Genes Involved in Huntington’s Disease. Cancers 2020, 12, 963.

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