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Updated: Oct 15, 2025
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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
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Epigenetic DNA Modifications Upregulate SPRY2 in Human Colorectal Cancers
Alexei J Stuckel1, Shuai Zeng2,3, Zhen Lyu2,3
1Department of Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, USA.
Cells
|October 23, 2021
Summary
Sprouty2 (SPRY2) is upregulated in colorectal cancer (CRC), contrary to its known tumor suppressor role. Epigenetic changes, including hypomethylation and increased 5hmC in the SPRY2 gene, drive this increased expression in CRC.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Sprouty2 (SPRY2) traditionally suppresses Receptor Tyrosine Kinase (RTK) signaling and is considered a tumor suppressor.
- Contrary to established roles, SPRY2 upregulation has been linked to augmented cancer phenotypes and Epithelial-Mesenchymal-Transition (EMT) in colorectal cancer (CRC).
Purpose of the Study:
- To investigate the epigenetic mechanisms regulating SPRY2 expression in colorectal cancer.
- To determine the role of DNA methylation (5mC) and hydroxymethylation (5hmC) in SPRY2 dysregulation in CRC.
Main Methods:
- Analysis of 5mC at four loci within the SPRY2 gene using Combined Bisulfite Restriction Analysis (COBRA).
- Evaluation of 5hmC data in the SPRY2 promoter and gene body.
- Bioinformatic analysis of SPRY2 transcriptomic and methylation data from TCGA and GEO databases.
- Western blotting to measure SPRY2 protein levels in CRC tumors and cells.
Main Results:
- Increased SPRY2 mRNA and protein expression were observed in CRC datasets and patient samples.
- Novel identification of SPRY2 promoter and gene body hypomethylation in colorectal adenocarcinomas.
- First-time observation of increased 5hmC deposition in the SPRY2 promoter region in CRC.
Conclusions:
- SPRY2 hypomethylation and increased promoter 5hmC are identified as potential drivers of SPRY2 upregulation in colorectal cancer.
- These epigenetic modifications may contribute to the pro-cancer effects of SPRY2 in CRC, challenging its traditional tumor suppressor function.
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