Sprouty4 is epigenetically upregulated in human colorectal cancer
Sprouty4 (SPRY4) has been frequently reported as a tumor suppressor and is therefore downregulated in various cancers. For the first time, we report that SPRY4 is epigenetically upregulated in colorectal cancer (CRC). In this study, we explored DNA methylation and hydroxymethylation levels of SPRY4...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2022.2145068 |
| _version_ | 1797678794596679680 |
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| author | Alexei J. Stuckel Shuai Zeng Zhen Lyu Wei Zhang Xu Zhang Urszula Dougherty Reba Mustafi Tripti Khare Qiong Zhang Trupti Joshi Marc Bissonnette Sharad Khare |
| author_facet | Alexei J. Stuckel Shuai Zeng Zhen Lyu Wei Zhang Xu Zhang Urszula Dougherty Reba Mustafi Tripti Khare Qiong Zhang Trupti Joshi Marc Bissonnette Sharad Khare |
| author_sort | Alexei J. Stuckel |
| collection | DOAJ |
| description | Sprouty4 (SPRY4) has been frequently reported as a tumor suppressor and is therefore downregulated in various cancers. For the first time, we report that SPRY4 is epigenetically upregulated in colorectal cancer (CRC). In this study, we explored DNA methylation and hydroxymethylation levels of SPRY4 in CRC cells and patient samples and correlated these findings with mRNA and protein expression levels. Three loci within the promoter region of SPRY4 were evaluated for 5mC levels in CRC using the combined bisulfite restriction analysis. In addition, hydroxymethylation levels within SPRY4 were measured in CRC patients. Lastly, DNA methylation and mRNA expression data were extracted from CRC patients in multiple high-throughput data repositories like Gene Expression Omnibus and The Cancer Genome Atlas. Combined in vitro and in silico analysis of promoter methylation levels of SPRY4 clearly demonstrates that the distal promoter region undergoes hypomethylation in CRC patients and is associated with increased expression. Moreover, a decrease in gene body hydroxymethylation and an increase in gene body methylation within the coding region of SPRY4 were found in CRC patients and correlated with increased expression. SPRY4 is epigenetically upregulated in CRC by promoter hypomethylation and hypermethylation within the gene body that warrants future investigation of atypical roles of this established tumor suppressor. |
| first_indexed | 2024-03-11T23:05:06Z |
| format | Article |
| id | doaj.art-01f8717e29a94b0eaa5128dbd992adb5 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:05:06Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-01f8717e29a94b0eaa5128dbd992adb52023-09-21T13:23:12ZengTaylor & Francis GroupEpigenetics1559-22941559-23082023-12-0118110.1080/15592294.2022.21450682145068Sprouty4 is epigenetically upregulated in human colorectal cancerAlexei J. Stuckel0Shuai Zeng1Zhen Lyu2Wei Zhang3Xu Zhang4Urszula Dougherty5Reba Mustafi6Tripti Khare7Qiong Zhang8Trupti Joshi9Marc Bissonnette10Sharad Khare11University of MissouriBond Life Sciences Center, University of MissouriBond Life Sciences Center, University of MissouriNorthwestern University Feinberg School of MedicineUniversity of IllinoisHepatology and Nutrition; the University of ChicagoHepatology and Nutrition; the University of ChicagoUniversity of MissouriUniversity of MissouriBond Life Sciences Center, University of MissouriHepatology and Nutrition; the University of ChicagoUniversity of MissouriSprouty4 (SPRY4) has been frequently reported as a tumor suppressor and is therefore downregulated in various cancers. For the first time, we report that SPRY4 is epigenetically upregulated in colorectal cancer (CRC). In this study, we explored DNA methylation and hydroxymethylation levels of SPRY4 in CRC cells and patient samples and correlated these findings with mRNA and protein expression levels. Three loci within the promoter region of SPRY4 were evaluated for 5mC levels in CRC using the combined bisulfite restriction analysis. In addition, hydroxymethylation levels within SPRY4 were measured in CRC patients. Lastly, DNA methylation and mRNA expression data were extracted from CRC patients in multiple high-throughput data repositories like Gene Expression Omnibus and The Cancer Genome Atlas. Combined in vitro and in silico analysis of promoter methylation levels of SPRY4 clearly demonstrates that the distal promoter region undergoes hypomethylation in CRC patients and is associated with increased expression. Moreover, a decrease in gene body hydroxymethylation and an increase in gene body methylation within the coding region of SPRY4 were found in CRC patients and correlated with increased expression. SPRY4 is epigenetically upregulated in CRC by promoter hypomethylation and hypermethylation within the gene body that warrants future investigation of atypical roles of this established tumor suppressor.http://dx.doi.org/10.1080/15592294.2022.2145068colorectal cancersprouty4gene expressiondna methylationdna hydroxymethylation |
| spellingShingle | Alexei J. Stuckel Shuai Zeng Zhen Lyu Wei Zhang Xu Zhang Urszula Dougherty Reba Mustafi Tripti Khare Qiong Zhang Trupti Joshi Marc Bissonnette Sharad Khare Sprouty4 is epigenetically upregulated in human colorectal cancer Epigenetics colorectal cancer sprouty4 gene expression dna methylation dna hydroxymethylation |
| title | Sprouty4 is epigenetically upregulated in human colorectal cancer |
| title_full | Sprouty4 is epigenetically upregulated in human colorectal cancer |
| title_fullStr | Sprouty4 is epigenetically upregulated in human colorectal cancer |
| title_full_unstemmed | Sprouty4 is epigenetically upregulated in human colorectal cancer |
| title_short | Sprouty4 is epigenetically upregulated in human colorectal cancer |
| title_sort | sprouty4 is epigenetically upregulated in human colorectal cancer |
| topic | colorectal cancer sprouty4 gene expression dna methylation dna hydroxymethylation |
| url | http://dx.doi.org/10.1080/15592294.2022.2145068 |
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