Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation
The epigenetic silencing of tumor suppressor genes in myelodysplastic syndromes (MDS) can potentially confer a growth advantage to individual cellular clones. Currently, the recommended treatment for patients with high-risk MDS is the methylation agent decitabine (DAC), a drug that can induce the re...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2017/4302320 |
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| _version_ | 1832562196547108864 |
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| author | Wen Zeng Hanjun Dai Ming Yan Xiaojun Cai Hong Luo Min Ke Zeming Liu |
| author_facet | Wen Zeng Hanjun Dai Ming Yan Xiaojun Cai Hong Luo Min Ke Zeming Liu |
| author_sort | Wen Zeng |
| collection | DOAJ |
| description | The epigenetic silencing of tumor suppressor genes in myelodysplastic syndromes (MDS) can potentially confer a growth advantage to individual cellular clones. Currently, the recommended treatment for patients with high-risk MDS is the methylation agent decitabine (DAC), a drug that can induce the reexpression of silenced tumor suppressor genes. We investigated the effects of DAC treatment on the myeloid MDS cell line SKM-1 and investigated the role of FOXO3A, a potentially tumor-suppressive transcription factor, by silencing its expression prior to DAC treatment. We found that FOXO3A exists in an inactive, hyperphosphorylated form in SKM-1 cells, but that DAC both induces FOXO3A expression and reactivates the protein by reducing its phosphorylation level. Furthermore, we show that this FOXO3A activation is responsible for the DAC-induced differentiation of SKM-1 cells into monocytes, as well as for SKM-1 cell cycle arrest, apoptosis, and autophagy. Collectively, these results suggest that FOXO3A reactivation may contribute to the therapeutic effects of DAC in MDS. |
| format | Article |
| id | doaj-art-811dc20b2fdc4d8cb37eb1852f9df41b |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-811dc20b2fdc4d8cb37eb1852f9df41b2025-02-03T01:23:12ZengWileyJournal of Immunology Research2314-88612314-71562017-01-01201710.1155/2017/43023204302320Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A ActivationWen Zeng0Hanjun Dai1Ming Yan2Xiaojun Cai3Hong Luo4Min Ke5Zeming Liu6Department of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaThe epigenetic silencing of tumor suppressor genes in myelodysplastic syndromes (MDS) can potentially confer a growth advantage to individual cellular clones. Currently, the recommended treatment for patients with high-risk MDS is the methylation agent decitabine (DAC), a drug that can induce the reexpression of silenced tumor suppressor genes. We investigated the effects of DAC treatment on the myeloid MDS cell line SKM-1 and investigated the role of FOXO3A, a potentially tumor-suppressive transcription factor, by silencing its expression prior to DAC treatment. We found that FOXO3A exists in an inactive, hyperphosphorylated form in SKM-1 cells, but that DAC both induces FOXO3A expression and reactivates the protein by reducing its phosphorylation level. Furthermore, we show that this FOXO3A activation is responsible for the DAC-induced differentiation of SKM-1 cells into monocytes, as well as for SKM-1 cell cycle arrest, apoptosis, and autophagy. Collectively, these results suggest that FOXO3A reactivation may contribute to the therapeutic effects of DAC in MDS.http://dx.doi.org/10.1155/2017/4302320 |
| spellingShingle | Wen Zeng Hanjun Dai Ming Yan Xiaojun Cai Hong Luo Min Ke Zeming Liu Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation Journal of Immunology Research |
| title | Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation |
| title_full | Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation |
| title_fullStr | Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation |
| title_full_unstemmed | Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation |
| title_short | Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation |
| title_sort | decitabine induced changes in human myelodysplastic syndrome cell line skm 1 are mediated by foxo3a activation |
| url | http://dx.doi.org/10.1155/2017/4302320 |
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