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PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma‐initiating cell properties via DNA methyltransferase 3A
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732353/ https://www.ncbi.nlm.nih.gov/pubmed/34214250 http://dx.doi.org/10.1002/1878-0261.13051 |
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author | Tanabe, Ryo Miyazono, Kohei Todo, Tomoki Saito, Nobuhito Iwata, Caname Komuro, Akiyoshi Sakai, Satoshi Raja, Erna Koinuma, Daizo Morikawa, Masato Westermark, Bengt Heldin, Carl‐Henrik |
author_facet | Tanabe, Ryo Miyazono, Kohei Todo, Tomoki Saito, Nobuhito Iwata, Caname Komuro, Akiyoshi Sakai, Satoshi Raja, Erna Koinuma, Daizo Morikawa, Masato Westermark, Bengt Heldin, Carl‐Henrik |
author_sort | Tanabe, Ryo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8732353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87323532022-01-11 PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma‐initiating cell properties via DNA methyltransferase 3A Tanabe, Ryo Miyazono, Kohei Todo, Tomoki Saito, Nobuhito Iwata, Caname Komuro, Akiyoshi Sakai, Satoshi Raja, Erna Koinuma, Daizo Morikawa, Masato Westermark, Bengt Heldin, Carl‐Henrik Mol Oncol Research Articles 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. John Wiley and Sons Inc. 2021-07-16 2022-01 /pmc/articles/PMC8732353/ /pubmed/34214250 http://dx.doi.org/10.1002/1878-0261.13051 Text en © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Tanabe, Ryo Miyazono, Kohei Todo, Tomoki Saito, Nobuhito Iwata, Caname Komuro, Akiyoshi Sakai, Satoshi Raja, Erna Koinuma, Daizo Morikawa, Masato Westermark, Bengt Heldin, Carl‐Henrik PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma‐initiating cell properties via DNA methyltransferase 3A |
title | PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma‐initiating cell properties via DNA methyltransferase 3A |
title_full | PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma‐initiating cell properties via DNA methyltransferase 3A |
title_fullStr | PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma‐initiating cell properties via DNA methyltransferase 3A |
title_full_unstemmed | PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma‐initiating cell properties via DNA methyltransferase 3A |
title_short | PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma‐initiating cell properties via DNA methyltransferase 3A |
title_sort | prrx1 induced by bmp signaling decreases tumorigenesis by epigenetically regulating glioma‐initiating cell properties via dna methyltransferase 3a |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732353/ https://www.ncbi.nlm.nih.gov/pubmed/34214250 http://dx.doi.org/10.1002/1878-0261.13051 |
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