Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation
| Autor: | Wen Zeng, Min Ke, Hanjun Dai, Hong Luo, Xiaojun Cai, Zeming Liu, Ming Yan |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Antimetabolites Antineoplastic Myeloid Cell cycle checkpoint Article Subject Cellular differentiation Immunology Decitabine Epigenetic Repression Biology Monocytes 03 medical and health sciences Cell Line Tumor Autophagy medicine Humans Immunology and Allergy Gene silencing Phosphorylation Transcription factor Regulation of gene expression Forkhead Box Protein O3 Cell Differentiation Cell Cycle Checkpoints General Medicine Molecular biology Gene Expression Regulation Neoplastic Leukemia Myeloid Acute 030104 developmental biology medicine.anatomical_structure Myelodysplastic Syndromes Azacitidine Cancer research lcsh:RC581-607 Research Article medicine.drug |
| Zdroj: | Journal of Immunology Research Journal of Immunology Research, Vol 2017 (2017) |
| ISSN: | 2314-7156 2314-8861 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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