RGD Reference Report - Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer. - Rat Genome Database

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

Authors: 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 
Citation: Stuckel AJ, etal., Cancers (Basel). 2020 Feb 26;12(3). pii: cancers12030539. doi: 10.3390/cancers12030539.
RGD ID: 151665323
Pubmed: PMID:32110952   (View Abstract at PubMed)
PMCID: PMC7139960   (View Article at PubMed Central)
DOI: DOI:10.3390/cancers12030539   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CXCR4Humancolorectal cancer  IEP mRNA:increased expression:colonic epithelium (human)RGD 
Cxcr4Ratcolorectal cancer  ISOCXCR4 (Homo sapiens)mRNA:increased expression:colonic epithelium (human)RGD 
Cxcr4Mousecolorectal cancer  ISOCXCR4 (Homo sapiens)mRNA:increased expression:colonic epithelium (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcr4  (C-X-C motif chemokine receptor 4)

Genes (Mus musculus)
Cxcr4  (C-X-C motif chemokine receptor 4)

Genes (Homo sapiens)
CXCR4  (C-X-C motif chemokine receptor 4)


Additional Information