SETD1A Promotes Proliferation of Castration-Resistant Prostate Cancer Cells via FOXM1 Transcription
Androgen deprivation therapy eventually leads to the development of castration-resistant prostate cancer (CRPC). Here, we demonstrate for the first time that the histone H3K4 methyltransferase SETD1A is a major regulator for the proliferation of metastatic CRPC (mCRPC). The expression of SETD1A was...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/7/1736 |
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| author | Liu Yang Mingli Jin Sung Jean Park Seung-Yong Seo Kwang Won Jeong |
| author_facet | Liu Yang Mingli Jin Sung Jean Park Seung-Yong Seo Kwang Won Jeong |
| author_sort | Liu Yang |
| collection | DOAJ |
| description | Androgen deprivation therapy eventually leads to the development of castration-resistant prostate cancer (CRPC). Here, we demonstrate for the first time that the histone H3K4 methyltransferase SETD1A is a major regulator for the proliferation of metastatic CRPC (mCRPC). The expression of SETD1A was significantly correlated with the survival rate of patients with prostate cancer. SETD1A, which is expressed at a higher level in mCRPC than in primary prostate cancer cells, promotes the expression of <i>FOXM1</i>, a gene encoding a cell proliferation-specific transcription factor. SETD1A is recruited to the promoter region of <i>FOXM1</i> (forkhead box M1) upon binding to E2F1, a protein that regulates the transcription of FOXM1 and contributes to the trimethylation of H3K4 in the <i>FOXM1</i> promoter region. In addition, SETD1A is essential for the expression of stem cell factor (e.g., <i>OCT4,</i> octamer-binding transcription factor 4) and stem cell formation in mCRPC, suggesting the importance of SETD1A expression in mCRPC tumor formation. Notably, poor prognosis is associated with high expression of the SETD1A–FOXM1 pair in clinical data sets. Therefore, our study suggests that SETD1A plays an important role in the proliferation of mCRPC by regulating <i>FOXM1</i> transcription. |
| first_indexed | 2024-03-10T18:48:40Z |
| format | Article |
| id | doaj.art-b3f25ce3657c42d58714838fc6e30391 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:48:40Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b3f25ce3657c42d58714838fc6e303912023-11-20T05:21:12ZengMDPI AGCancers2072-66942020-06-01127173610.3390/cancers12071736SETD1A Promotes Proliferation of Castration-Resistant Prostate Cancer Cells via FOXM1 TranscriptionLiu Yang0Mingli Jin1Sung Jean Park2Seung-Yong Seo3Kwang Won Jeong4Gachon Research Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaGachon Research Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaGachon Research Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaGachon Research Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaGachon Research Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaAndrogen deprivation therapy eventually leads to the development of castration-resistant prostate cancer (CRPC). Here, we demonstrate for the first time that the histone H3K4 methyltransferase SETD1A is a major regulator for the proliferation of metastatic CRPC (mCRPC). The expression of SETD1A was significantly correlated with the survival rate of patients with prostate cancer. SETD1A, which is expressed at a higher level in mCRPC than in primary prostate cancer cells, promotes the expression of <i>FOXM1</i>, a gene encoding a cell proliferation-specific transcription factor. SETD1A is recruited to the promoter region of <i>FOXM1</i> (forkhead box M1) upon binding to E2F1, a protein that regulates the transcription of FOXM1 and contributes to the trimethylation of H3K4 in the <i>FOXM1</i> promoter region. In addition, SETD1A is essential for the expression of stem cell factor (e.g., <i>OCT4,</i> octamer-binding transcription factor 4) and stem cell formation in mCRPC, suggesting the importance of SETD1A expression in mCRPC tumor formation. Notably, poor prognosis is associated with high expression of the SETD1A–FOXM1 pair in clinical data sets. Therefore, our study suggests that SETD1A plays an important role in the proliferation of mCRPC by regulating <i>FOXM1</i> transcription.https://www.mdpi.com/2072-6694/12/7/1736SETD1AFOXM1prostate cancercastration-resistant |
| spellingShingle | Liu Yang Mingli Jin Sung Jean Park Seung-Yong Seo Kwang Won Jeong SETD1A Promotes Proliferation of Castration-Resistant Prostate Cancer Cells via FOXM1 Transcription Cancers SETD1A FOXM1 prostate cancer castration-resistant |
| title | SETD1A Promotes Proliferation of Castration-Resistant Prostate Cancer Cells via FOXM1 Transcription |
| title_full | SETD1A Promotes Proliferation of Castration-Resistant Prostate Cancer Cells via FOXM1 Transcription |
| title_fullStr | SETD1A Promotes Proliferation of Castration-Resistant Prostate Cancer Cells via FOXM1 Transcription |
| title_full_unstemmed | SETD1A Promotes Proliferation of Castration-Resistant Prostate Cancer Cells via FOXM1 Transcription |
| title_short | SETD1A Promotes Proliferation of Castration-Resistant Prostate Cancer Cells via FOXM1 Transcription |
| title_sort | setd1a promotes proliferation of castration resistant prostate cancer cells via foxm1 transcription |
| topic | SETD1A FOXM1 prostate cancer castration-resistant |
| url | https://www.mdpi.com/2072-6694/12/7/1736 |
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