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Correction published on 23 October 2020, see Cancers 2020, 12(11), 3104.
Article

Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer

1
Department of Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, USA
2
Department of Preventive Medicine and The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
3
Department of Medicine, University of Illinois, Chicago, IL 60607, USA
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Bond Life Sciences Center, University of Missouri, Columbia, MO 65201, USA
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Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO 65201, USA
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Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition, The University of Chicago, Chicago, IL 60637, USA
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Institute for Data Science and Informatics, University of Missouri, Columbia, MO 65211, USA
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Department of Health Management and Informatics, School of Medicine, University of Missouri, Columbia, MO 65212, USA
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Harry S. Truman Memorial Veterans’ Hospital, Columbia, MO 65201, USA
*
Author to whom correspondence should be addressed.
S.K. and M.B. share senior authorship.
Cancers 2020, 12(3), 539; https://doi.org/10.3390/cancers12030539
Received: 7 January 2020 / Revised: 19 February 2020 / Accepted: 24 February 2020 / Published: 26 February 2020
In colorectal cancer (CRC), upregulation of the C-X-C motif chemokine receptor 4 (CXCR4) is correlated with metastasis and poor prognosis, highlighting the need to further elucidate CXCR4’s regulation in CRC. For the first time, DNA methylation and 5-hydroxymethylcytosine aberrations were investigated to better understand the epigenetic regulation of CXCR4 in CRC. CXCR4 expression levels were measured using qPCR and immunoblotting in normal colon tissues, primary colon cancer tissues and CRC cell lines. Publicly available RNA-seq and methylation data from The Cancer Genome Atlas (TCGA) were extracted from tumors from CRC patients. The DNA methylation status spanning CXCR4 gene was evaluated using combined bisulfite restriction analysis (COBRA). The methylation status in the CXCR4 gene body was analyzed using previously performed nano-hmC-seal data from colon cancers and adjacent normal colonic mucosa. CXCR4 expression levels were significantly increased in tumor stromal cells and in tumor colonocytes, compared to matched cell types from adjacent normal-appearing mucosa. CXCR4 promoter methylation was detected in a minority of colorectal tumors in the TCGA. The CpG island of the CXCR4 promoter showed increased methylation in three of four CRC cell lines. CXCR4 protein expression differences were also notable between microsatellite stable (MSS) and microsatellite instable (MSI) tumor cell lines. While differential methylation was not detected in CXCR4, enrichment of 5-hydroxymethylcytosine (5hmC) in CXCR4 gene bodies in CRC was observed compared to adjacent mucosa. View Full-Text
Keywords: colorectal cancer; DNA methylation; epigenetic regulation; CXCR4 gene expression; 5-hydroxymethylcytosine colorectal cancer; DNA methylation; epigenetic regulation; CXCR4 gene expression; 5-hydroxymethylcytosine
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MDPI and ACS Style

Stuckel, A.J.; Zhang, W.; Zhang, X.; Zeng, S.; Dougherty, U.; Mustafi, R.; Zhang, Q.; Perreand, E.; Khare, T.; Joshi, T.; West-Szymanski, D.C.; Bissonnette, M.; Khare, S. Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer. Cancers 2020, 12, 539. https://doi.org/10.3390/cancers12030539

AMA Style

Stuckel AJ, Zhang W, Zhang X, Zeng S, Dougherty U, Mustafi R, Zhang Q, Perreand E, Khare T, Joshi T, West-Szymanski DC, Bissonnette M, Khare S. Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer. Cancers. 2020; 12(3):539. https://doi.org/10.3390/cancers12030539

Chicago/Turabian Style

Stuckel, Alexei J., Wei Zhang, Xu Zhang, Shuai Zeng, Urszula Dougherty, Reba Mustafi, Qiong Zhang, Elsa Perreand, Tripti Khare, Trupti Joshi, Diana C. West-Szymanski, Marc Bissonnette, and Sharad Khare. 2020. "Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer" Cancers 12, no. 3: 539. https://doi.org/10.3390/cancers12030539

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