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

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 investigat...

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Autores principales: Stuckel, Alexei J., Zhang, Wei, Zhang, Xu, Zeng, Shuai, Dougherty, Urszula, Mustafi, Reba, Zhang, Qiong, Perreand, Elsa, Khare, Tripti, Joshi, Trupti, West-Szymanski, Diana C., Bissonnette, Marc, Khare, Sharad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139960/
https://www.ncbi.nlm.nih.gov/pubmed/32110952
http://dx.doi.org/10.3390/cancers12030539
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author Stuckel, Alexei J.
Zhang, Wei
Zhang, Xu
Zeng, Shuai
Dougherty, Urszula
Mustafi, Reba
Zhang, Qiong
Perreand, Elsa
Khare, Tripti
Joshi, Trupti
West-Szymanski, Diana C.
Bissonnette, Marc
Khare, Sharad
author_facet Stuckel, Alexei J.
Zhang, Wei
Zhang, Xu
Zeng, Shuai
Dougherty, Urszula
Mustafi, Reba
Zhang, Qiong
Perreand, Elsa
Khare, Tripti
Joshi, Trupti
West-Szymanski, Diana C.
Bissonnette, Marc
Khare, Sharad
author_sort Stuckel, Alexei J.
collection PubMed
description 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.
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spelling pubmed-71399602020-04-13 Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer Stuckel, Alexei J. Zhang, Wei Zhang, Xu Zeng, Shuai Dougherty, Urszula Mustafi, Reba Zhang, Qiong Perreand, Elsa Khare, Tripti Joshi, Trupti West-Szymanski, Diana C. Bissonnette, Marc Khare, Sharad Cancers (Basel) Article 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. MDPI 2020-02-26 /pmc/articles/PMC7139960/ /pubmed/32110952 http://dx.doi.org/10.3390/cancers12030539 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Stuckel, Alexei J.
Zhang, Wei
Zhang, Xu
Zeng, Shuai
Dougherty, Urszula
Mustafi, Reba
Zhang, Qiong
Perreand, Elsa
Khare, Tripti
Joshi, Trupti
West-Szymanski, Diana C.
Bissonnette, Marc
Khare, Sharad
Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer
title Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer
title_full Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer
title_fullStr Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer
title_full_unstemmed Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer
title_short Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer
title_sort enhanced cxcr4 expression associates with increased gene body 5-hydroxymethylcytosine modification but not decreased promoter methylation in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139960/
https://www.ncbi.nlm.nih.gov/pubmed/32110952
http://dx.doi.org/10.3390/cancers12030539
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