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

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

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Article in NPJ precision oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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8 authors.

Tong Chen *Key Laboratory of Neonatal Disease, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China.

Huiyao Chen *Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China.

Mingyang Xia *Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Fudan University, Shanghai, China.

Yunfei LiaoCenter for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China.

Hao LiDepartment of Neurosurgery, Children's Hospital of Fudan University, Shanghai, China.

Xinran DongCenter for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. xrdong@fudan.edu.cn.

Yifeng LinKey Laboratory of Neonatal Disease, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China. irenelin2002@hotmail.com.ORCID http://orcid.org/0000-0003-4411-8388

Wenhao ZhouDivision of Neonatology and Center for Newborn Care, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82203293

6 · The paper itself

Abstract

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.

Identifiers

PMID39794402

DOI10.1038/s41698-024-00792-7

PMCPMC11723958

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.