Evidence map›Paper›PMID 39390804›Full record

ArticleCNS neuroscience & therapeutics2024

SOXC Enhances NGN2-Mediated Reprogramming of Glioblastoma Cells Into Neuron-Like Cells by Modulating RhoA and RAC1/CDC42 Pathway Activity.

Jianjing Yang, Xiaohong Zhu, Fan Wang, Zhen Chen, Ying Zhang, Jiawei Chen, Haoqi Ni, Chun-Li Zhang, Qichuan Zhuge

Abstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2024. 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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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Jianjing YangDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID 0000-0001-9416-1195
Xiaohong ZhuDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Fan WangDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Zhen ChenDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Ying ZhangDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jiawei ChenDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Haoqi NiDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Chun-Li ZhangDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Qichuan ZhugeDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Funding

National Natural Science Foundation of China 82103216National Natural Science Foundation of China 82271345
6 · The paper itself

Abstract

backgroundGlioblastoma represents the most frequently diagnosed malignant neoplasm within the central nervous system. Human glioblastoma cells can be phenotypically reprogrammed into neuron-like cells through the forced expression of NEUROG2 and SOXC factors. NEUROG2 serves as a pioneer factor, establishing an initial framework for this transformation. However, the specific role of SOXC factors has not been fully elucidated.

methodsIn this study, we used ChIP-seq to determine the potential target gene of NGN2. RNA-seq has been used to evaluate the transcriptional change during NGN2-SOX11-mediated neuron reprogramming. Immunofluorescence was used to determine the neuron reprogramming efficacy and cell proliferation ability. ChIP-qPCR, Co-IP, and Western Blot were performed to investigate the mechanism.

resultsOur findings reveal that SOXC factors, in contrast to their previously identified function as transcriptional activators, act as transcriptional repressors. They achieve this by recruiting TRIM28 to suppress the expression of ECT2, a RhoGEF. This suppression results in the differential regulation of RhoA, RAC1, and CDC42 activities throughout the reprogramming process. We further establish that small molecules targeting RhoA and its effectors can substitute for SOXC factors in facilitating the neuronal reprogramming of glioblastoma cells.

conclusionThese results underscore the pivotal role of SOXC factors' transcriptional repression and illuminate one of their specific downstream targets.

Indexed as

Basic Helix-Loop-Helix Proteinscdc42 GTP-Binding ProteinCellular ReprogrammingGlioblastomaNerve Tissue ProteinsNeuronsrac1 GTP-Binding ProteinrhoA GTP-Binding ProteinSignal TransductionSOXC Transcription FactorsBrain NeoplasmsCell Line, TumorHumansBasic Helix-Loop-Helix Proteinscdc42 GTP-Binding ProteinCDC42 protein, humanNerve Tissue ProteinsNEUROG2 protein, humanrac1 GTP-Binding ProteinRAC1 protein, humanrhoA GTP-Binding ProteinRHOA protein, humanSOX11 protein, humanSOXC Transcription FactorsECT2glioblastomaNGN2RAC1/CDC42RhoASOX4/11

Identifiers

PMID39390804
PMCPMC11467166

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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.