Expression of UDP Glucuronosyltransferases 2B15 and 2B17 is associated with methylation status in prostate cancer cells
Studies have suggested that abrogated expression of detoxification enzymes, UGT2B15 and UGT2B17, are associated with prostate tumour risk and progression. We investigated the role of EGF on the expression of these enzymes since it interacts with signalling pathways to also affect prostate tumour pro...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-03-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2020.1795601 |
| _version_ | 1797678839544938496 |
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| author | Farideh Shafiee-Kermani Skyla T. Carney Dereje Jima Utibe C. Utin LaNeisha B. Farrar Melvin O. Oputa Marcono R. Hines H. Karimi Kinyamu Kevin W. Trotter Trevor K. Archer Cathrine Hoyo Beverly H. Koller Stephen J. Freedland Delores J. Grant |
| author_facet | Farideh Shafiee-Kermani Skyla T. Carney Dereje Jima Utibe C. Utin LaNeisha B. Farrar Melvin O. Oputa Marcono R. Hines H. Karimi Kinyamu Kevin W. Trotter Trevor K. Archer Cathrine Hoyo Beverly H. Koller Stephen J. Freedland Delores J. Grant |
| author_sort | Farideh Shafiee-Kermani |
| collection | DOAJ |
| description | Studies have suggested that abrogated expression of detoxification enzymes, UGT2B15 and UGT2B17, are associated with prostate tumour risk and progression. We investigated the role of EGF on the expression of these enzymes since it interacts with signalling pathways to also affect prostate tumour progression and is additionally associated with decreased DNA methylation. The expression of UGT2B15, UGT2B17, de novo methyltransferases, DNMT3A and DNMT3B was assessed in prostate cancer cells (LNCaP) treated with EGF, an EGFR inhibitor PD16893, and the methyltransferase inhibitor, 5-azacytidine, respectively. The results showed that EGF treatment decreased levels of expression of all four genes and that their expression was reversed by PD16893. Treatment with 5-azacytidine, markedly decreased expression of UGT2B15 and UGT2B17 over 85% as well as significantly decreased expression of DNMT3B, but not the expression of DNMT3A. DNMT3B siRNA treated LNCaP cells had decreased expression of UGT2B15 and UGT2B17, while DNMT3A siRNA treated cells had only moderately decreased UGT2B15 expression. Treatment with DNMT methyltransferase inhibitor, RG108, significantly decreased UGT2B17 expression. Additionally, methylation differences between prostate cancer samples and benign prostate samples from an Illumina 450K Methylation Array study were assessed. The results taken together suggest that hypomethylation of the UGT2B15 and UGT2B17 genes contributes to increased risk of prostate cancer and may provide a putative biomarker or epigenetic target for chemotherapeutics. Mechanistic studies are warranted to determine the role of the methylation marks in prostate cancer. |
| first_indexed | 2024-03-11T23:05:49Z |
| format | Article |
| id | doaj.art-b07d19108d254966ae0dcb681885e3bb |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:05:49Z |
| publishDate | 2021-03-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-b07d19108d254966ae0dcb681885e3bb2023-09-21T13:09:24ZengTaylor & Francis GroupEpigenetics1559-22941559-23082021-03-0116328929910.1080/15592294.2020.17956011795601Expression of UDP Glucuronosyltransferases 2B15 and 2B17 is associated with methylation status in prostate cancer cellsFarideh Shafiee-Kermani0Skyla T. Carney1Dereje Jima2Utibe C. Utin3LaNeisha B. Farrar4Melvin O. Oputa5Marcono R. Hines6H. Karimi Kinyamu7Kevin W. Trotter8Trevor K. Archer9Cathrine Hoyo10Beverly H. Koller11Stephen J. Freedland12Delores J. Grant13North Carolina Central UniversityNorth Carolina Central UniversityNorth Carolina State UniversityNorth Carolina Central UniversityNorth Carolina Central UniversityNorth Carolina Central UniversityNorth Carolina Central UniversityNational Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle ParkNational Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle ParkNational Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle ParkNorth Carolina State UniversityUniversity of North Carolina at Chapel HillCedars-Sinai Health System Center for Integrated Research on Cancer and LifestylesNorth Carolina State UniversityStudies have suggested that abrogated expression of detoxification enzymes, UGT2B15 and UGT2B17, are associated with prostate tumour risk and progression. We investigated the role of EGF on the expression of these enzymes since it interacts with signalling pathways to also affect prostate tumour progression and is additionally associated with decreased DNA methylation. The expression of UGT2B15, UGT2B17, de novo methyltransferases, DNMT3A and DNMT3B was assessed in prostate cancer cells (LNCaP) treated with EGF, an EGFR inhibitor PD16893, and the methyltransferase inhibitor, 5-azacytidine, respectively. The results showed that EGF treatment decreased levels of expression of all four genes and that their expression was reversed by PD16893. Treatment with 5-azacytidine, markedly decreased expression of UGT2B15 and UGT2B17 over 85% as well as significantly decreased expression of DNMT3B, but not the expression of DNMT3A. DNMT3B siRNA treated LNCaP cells had decreased expression of UGT2B15 and UGT2B17, while DNMT3A siRNA treated cells had only moderately decreased UGT2B15 expression. Treatment with DNMT methyltransferase inhibitor, RG108, significantly decreased UGT2B17 expression. Additionally, methylation differences between prostate cancer samples and benign prostate samples from an Illumina 450K Methylation Array study were assessed. The results taken together suggest that hypomethylation of the UGT2B15 and UGT2B17 genes contributes to increased risk of prostate cancer and may provide a putative biomarker or epigenetic target for chemotherapeutics. Mechanistic studies are warranted to determine the role of the methylation marks in prostate cancer.http://dx.doi.org/10.1080/15592294.2020.1795601human udp-glucuronosyltransferases 2bprostate cancermethylationdna methyltransferasesepigenetic regulation |
| spellingShingle | Farideh Shafiee-Kermani Skyla T. Carney Dereje Jima Utibe C. Utin LaNeisha B. Farrar Melvin O. Oputa Marcono R. Hines H. Karimi Kinyamu Kevin W. Trotter Trevor K. Archer Cathrine Hoyo Beverly H. Koller Stephen J. Freedland Delores J. Grant Expression of UDP Glucuronosyltransferases 2B15 and 2B17 is associated with methylation status in prostate cancer cells Epigenetics human udp-glucuronosyltransferases 2b prostate cancer methylation dna methyltransferases epigenetic regulation |
| title | Expression of UDP Glucuronosyltransferases 2B15 and 2B17 is associated with methylation status in prostate cancer cells |
| title_full | Expression of UDP Glucuronosyltransferases 2B15 and 2B17 is associated with methylation status in prostate cancer cells |
| title_fullStr | Expression of UDP Glucuronosyltransferases 2B15 and 2B17 is associated with methylation status in prostate cancer cells |
| title_full_unstemmed | Expression of UDP Glucuronosyltransferases 2B15 and 2B17 is associated with methylation status in prostate cancer cells |
| title_short | Expression of UDP Glucuronosyltransferases 2B15 and 2B17 is associated with methylation status in prostate cancer cells |
| title_sort | expression of udp glucuronosyltransferases 2b15 and 2b17 is associated with methylation status in prostate cancer cells |
| topic | human udp-glucuronosyltransferases 2b prostate cancer methylation dna methyltransferases epigenetic regulation |
| url | http://dx.doi.org/10.1080/15592294.2020.1795601 |
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