Reference - Detail
| RRC ID | 81379 |
|---|---|
| Author | Tanabe R, Miyazono K, Todo T, Saito N, Iwata C, Komuro A, Sakai S, Raja E, Koinuma D, Morikawa M, Westermark B, Heldin CH. |
| Title | PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma-initiating cell properties via DNA methyltransferase 3A. |
| Journal | 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. |
| Volume | 16(1) |
| Pages | 269-288 |
| Published | 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Peer-review(Publons) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | pENTR4-H1 (RDB04395) CSII-EF-RfA (RDB04387) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |