論文 - 詳細
| RRC ID | 81379 |
|---|---|
| 著者 | Tanabe R, Miyazono K, Todo T, Saito N, Iwata C, Komuro A, Sakai S, Raja E, Koinuma D, Morikawa M, Westermark B, Heldin CH. |
| タイトル | PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma-initiating cell properties via DNA methyltransferase 3A. |
| ジャーナル | Mol Oncol |
| Abstract |
Glioma-initiating cells (GICs), a major source of glioblastoma recurrence, are characterized by the expression of neural stem cell markers and the ability to grow by forming nonadherent spheres under serum-free conditions. Bone morphogenetic proteins (BMPs), members of the transforming growth factor-β family, induce differentiation of GICs and suppress their tumorigenicity. However, the mechanisms underlying the BMP-induced loss of GIC stemness have not been fully elucidated. Here, we show that paired related homeobox 1 (PRRX1) induced by BMPs decreases the CD133-positive GIC population and inhibits tumorigenic activity of GICs in vivo. Of the two splice isoforms of PRRX1, the longer isoform, pmx-1b, but not the shorter isoform, pmx-1a, induces GIC differentiation. Upon BMP stimulation, pmx-1b interacts with the DNA methyltransferase DNMT3A and induces promoter methylation of the PROM1 gene encoding CD133. Silencing DNMT3A maintains PROM1 expression and increases the CD133-positive GIC population. Thus, pmx-1b promotes loss of stem cell-like properties of GICs through region-specific epigenetic regulation of CD133 expression by recruiting DNMT3A, which is associated with decreased tumorigenicity of GICs. |
| 巻・号 | 16(1) |
| ページ | 269-288 |
| 公開日 | 2022-1-1 |
| DOI | 10.1002/1878-0261.13051 |
| PMID | 34214250 |
| PMC | PMC8732353 |
| MeSH | Brain Neoplasms* / genetics Brain Neoplasms* / metabolism Carcinogenesis / genetics Carcinogenesis / metabolism DNA Methyltransferase 3A Epigenesis, Genetic Glioblastoma* / genetics Glioblastoma* / metabolism Glioma* / genetics Homeodomain Proteins / genetics Homeodomain Proteins / metabolism Humans Neoplastic Stem Cells / metabolism |
| IF | 6.574 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Peer-review(Publons) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pENTR4-H1 (RDB04395) CSII-EF-RfA (RDB04387) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |