Epigenetic DNA Modifications Upregulate SPRY2 in Human Colorectal Cancers
Conventional wisdom is that Sprouty2 (SPRY2), a suppressor of Receptor Tyrosine Kinase (RTK) signaling, functions as a tumor suppressor and is downregulated in many solid tumors. We reported, for the first time, that increased expression of SPRY2 augments cancer phenotype and Epithelial-Mesenchymal-...
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MDPI AG
2021-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2632 |
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| author | Alexei J. Stuckel Shuai Zeng Zhen Lyu Wei Zhang Xu Zhang Urszula Dougherty Reba Mustafi Qiong Zhang Trupti Joshi Marc Bissonnette Samrat Roy Choudhury Sharad Khare |
| author_facet | Alexei J. Stuckel Shuai Zeng Zhen Lyu Wei Zhang Xu Zhang Urszula Dougherty Reba Mustafi Qiong Zhang Trupti Joshi Marc Bissonnette Samrat Roy Choudhury Sharad Khare |
| author_sort | Alexei J. Stuckel |
| collection | DOAJ |
| description | Conventional wisdom is that Sprouty2 (SPRY2), a suppressor of Receptor Tyrosine Kinase (RTK) signaling, functions as a tumor suppressor and is downregulated in many solid tumors. We reported, for the first time, that increased expression of SPRY2 augments cancer phenotype and Epithelial-Mesenchymal-Transition (EMT) in colorectal cancer (CRC). In this report, we assessed epigenetic DNA modifications that regulate SPRY2 expression in CRC. A total of 4 loci within <i>SPRY2</i> were evaluated for 5mC using Combined Bisulfite Restriction Analysis (COBRA). Previously sequenced 5hmC nano-hmC seal data within <i>SPRY2</i> promoter and gene body were evaluated in CRC. Combined bioinformatics analyses of SPRY2 CRC transcripts by RNA-seq/microarray and 450K methyl-array data archived in The Cancer Genome Atlas (TCGA) and GEO database were performed. SPRY2 protein in CRC tumors and cells was measured by Western blotting. Increased SPRY2 mRNA was observed across several CRC datasets and increased protein expression was observed among CRC patient samples. For the first time, <i>SPRY2</i> hypomethylation was identified in adenocarcinomas in the promoter and gene body. We also revealed, for the first time, increases of 5hmC deposition in the promoter region of <i>SPRY2</i> in CRC. <i>SPRY2</i> promoter hypomethylation and increased 5hmC may play an influential role in upregulating SPRY2 in CRC. |
| first_indexed | 2024-03-10T06:39:36Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:39:36Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7fdf92d5c6ff403b94cd6780e8fa8c7c2023-11-22T17:46:42ZengMDPI AGCells2073-44092021-10-011010263210.3390/cells10102632Epigenetic DNA Modifications Upregulate SPRY2 in Human Colorectal CancersAlexei J. Stuckel0Shuai Zeng1Zhen Lyu2Wei Zhang3Xu Zhang4Urszula Dougherty5Reba Mustafi6Qiong Zhang7Trupti Joshi8Marc Bissonnette9Samrat Roy Choudhury10Sharad Khare11Department of Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, USABond Life Sciences Center, University of Missouri, Columbia, MO 65201, USABond Life Sciences Center, University of Missouri, Columbia, MO 65201, USAThe Robert H. Lurie Comprehensive Cancer Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USADepartment of Medicine, University of Illinois, Chicago, IL 60607, USADepartment of Medicine, Section of Gastroenterology, Hepatology and Nutrition, The University of Chicago, Chicago, IL 60637, USADepartment of Medicine, Section of Gastroenterology, Hepatology and Nutrition, The University of Chicago, Chicago, IL 60637, USADepartment of Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, USABond Life Sciences Center, University of Missouri, Columbia, MO 65201, USADepartment of Medicine, Section of Gastroenterology, Hepatology and Nutrition, The University of Chicago, Chicago, IL 60637, USADepartment of Pediatrics, Arkansas Children’s Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USADepartment of Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, USAConventional wisdom is that Sprouty2 (SPRY2), a suppressor of Receptor Tyrosine Kinase (RTK) signaling, functions as a tumor suppressor and is downregulated in many solid tumors. We reported, for the first time, that increased expression of SPRY2 augments cancer phenotype and Epithelial-Mesenchymal-Transition (EMT) in colorectal cancer (CRC). In this report, we assessed epigenetic DNA modifications that regulate SPRY2 expression in CRC. A total of 4 loci within <i>SPRY2</i> were evaluated for 5mC using Combined Bisulfite Restriction Analysis (COBRA). Previously sequenced 5hmC nano-hmC seal data within <i>SPRY2</i> promoter and gene body were evaluated in CRC. Combined bioinformatics analyses of SPRY2 CRC transcripts by RNA-seq/microarray and 450K methyl-array data archived in The Cancer Genome Atlas (TCGA) and GEO database were performed. SPRY2 protein in CRC tumors and cells was measured by Western blotting. Increased SPRY2 mRNA was observed across several CRC datasets and increased protein expression was observed among CRC patient samples. For the first time, <i>SPRY2</i> hypomethylation was identified in adenocarcinomas in the promoter and gene body. We also revealed, for the first time, increases of 5hmC deposition in the promoter region of <i>SPRY2</i> in CRC. <i>SPRY2</i> promoter hypomethylation and increased 5hmC may play an influential role in upregulating SPRY2 in CRC.https://www.mdpi.com/2073-4409/10/10/2632colorectal cancerDNA methylationepigenetic regulationSPRY2 gene expression5-hydroxymethylcytosineCTCF transcription factor |
| spellingShingle | Alexei J. Stuckel Shuai Zeng Zhen Lyu Wei Zhang Xu Zhang Urszula Dougherty Reba Mustafi Qiong Zhang Trupti Joshi Marc Bissonnette Samrat Roy Choudhury Sharad Khare Epigenetic DNA Modifications Upregulate SPRY2 in Human Colorectal Cancers Cells colorectal cancer DNA methylation epigenetic regulation SPRY2 gene expression 5-hydroxymethylcytosine CTCF transcription factor |
| title | Epigenetic DNA Modifications Upregulate SPRY2 in Human Colorectal Cancers |
| title_full | Epigenetic DNA Modifications Upregulate SPRY2 in Human Colorectal Cancers |
| title_fullStr | Epigenetic DNA Modifications Upregulate SPRY2 in Human Colorectal Cancers |
| title_full_unstemmed | Epigenetic DNA Modifications Upregulate SPRY2 in Human Colorectal Cancers |
| title_short | Epigenetic DNA Modifications Upregulate SPRY2 in Human Colorectal Cancers |
| title_sort | epigenetic dna modifications upregulate spry2 in human colorectal cancers |
| topic | colorectal cancer DNA methylation epigenetic regulation SPRY2 gene expression 5-hydroxymethylcytosine CTCF transcription factor |
| url | https://www.mdpi.com/2073-4409/10/10/2632 |
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