Scholarlink

<p>Medulloblastoma (MB) is an aggressive pediatric brain tumor with distinct molecular heterogeneity. Identifying subtype-specific signatures within Group 3 and Group 4 remains challenging due to shared cytogenetic alterations and limitations of conventional differential gene expression analysis. To uncover the underlying molecular signatures and hidden regulators, we used the Cavalli transcriptomic profile of 470 Group 3 and Group 4 MB patients to reconstruct subtype-specific regulatory networks. A strong upregulation of the ribosomal pathway was linked to <i>MYC</i> amplification in Group 3, with Nucleophosmin 1 (<i>NPM1</i>) emerging as a key regulator. <i>NPM1</i> upregulation defined a subset of Group3 and Group4 patients with poor prognosis. Inhibition of NPM1 led to apoptosis, reduced c-Myc stability, and impaired translation in <i>MYC</i>-amplified Group 3 MB cells. Together, our findings highlight NPM1 as a promising therapeutic target and provide new insights into the regulatory mechanisms in MB.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

In-depth inference of transcriptional regulatory networks reveals NPM1 as a therapeutic ribosomal regulator in MYC-amplified medulloblastoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月10日

查看全文
  • Tong Chen,
  • Huiyao Chen,
  • Mingyang Xia,
  • Yunfei Liao,
  • Hao Li,
  • Xinran Dong,
  • Yifeng Lin,
  • Wenhao Zhou

摘要

Medulloblastoma (MB) is an aggressive pediatric brain tumor with distinct molecular heterogeneity. Identifying subtype-specific signatures within Group 3 and Group 4 remains challenging due to shared cytogenetic alterations and limitations of conventional differential gene expression analysis. To uncover the underlying molecular signatures and hidden regulators, we used the Cavalli transcriptomic profile of 470 Group 3 and Group 4 MB patients to reconstruct subtype-specific regulatory networks. A strong upregulation of the ribosomal pathway was linked to MYC amplification in Group 3, with Nucleophosmin 1 (NPM1) emerging as a key regulator. NPM1 upregulation defined a subset of Group3 and Group4 patients with poor prognosis. Inhibition of NPM1 led to apoptosis, reduced c-Myc stability, and impaired translation in MYC-amplified Group 3 MB cells. Together, our findings highlight NPM1 as a promising therapeutic target and provide new insights into the regulatory mechanisms in MB.