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  • PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma-initiating cell properties via DNA methyltransferase 3A.

PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma-initiating cell properties via DNA methyltransferase 3A.

Molecular oncology (2021-07-03)
Ryo Tanabe, Kohei Miyazono, Tomoki Todo, Nobuhito Saito, Caname Iwata, Akiyoshi Komuro, Satoshi Sakai, Erna Raja, Daizo Koinuma, Masato Morikawa, Bengt Westermark, Carl-Henrik Heldin
摘要

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.

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单克隆抗-FLAG® M2 小鼠抗, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
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抗-α-微管蛋白抗体,小鼠单克隆, clone DM1A, purified from hybridoma cell culture
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货号包装规格是否有货价格数量
5 g
有货
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¥533.71
100 g
有货
详情...
¥858.69
500 g
预计发货时间 2025年10月15日
详情...
¥1,522.44