Lentinan suppresses the progression of neuroblastoma by inhibiting FOS-mediated transcription activation of VRK1 to stabilize p53 protein.

IF 7 2区生物学 Q1 CELL BIOLOGY Cell Death Discovery Pub Date : 2025-03-15 DOI:10.1038/s41420-025-02315-0

Zhang Zhao, Jiahao Li, Liyu Zhang, Jiayu Wang, Dian Li, Manna Zheng, Zijie Ye, Tianyou Yang, Yan Zou, Jing Pan, Hui Xu, Huijuan Zeng, Chao Hu

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Abstract

Neuroblastoma (NB) is a common malignant and solid pediatric tumor with unfavorable prognosis. Although studies have shown the anti-tumor efficacy of lentinan (LNT), molecular mechanism that contribute to the anti-tumor effect on NB remains unclear. The aim of this study is to unmask the anti-tumor role of LNT in NB and the specific molecular mechanism. At first, the in vivo experiments were conducted and the results indicated that LNT could suppress tumor growth in NB. Subsequent cellular functional assays unveiled that LNT treatment could efficiently decrease NB cell viability, induce cell cycle stagnation at G0/G1 phase, increase the apoptosis rate, and weaken the migrating and invasive abilities. Furthermore, LNT resulted in a significant downregulation of FOS expression. FOS overexpression recovered the growth, migration and invasion of NB cells suppressed by LNT treatment. Mechanism investigations revealed that FOS interacted with JUND to transcriptionally activate VRK1. Moreover, VRK1 downregulated p53 protein via inducing the phosphorylation of p53 at site 291-393. In summary, this study reveals a novel molecular pathway by which LNT exerts tumor-suppressing functions in NB.

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香菇多糖通过抑制fos介导的VRK1转录激活来稳定p53蛋白，从而抑制神经母细胞瘤的进展。

神经母细胞瘤（NB）是一种常见的儿童恶性实体肿瘤，预后不良。虽然研究表明香菇多糖（LNT）具有抗肿瘤作用，但其对NB抗肿瘤作用的分子机制尚不清楚。本研究旨在揭示LNT在NB中的抗肿瘤作用及其具体的分子机制。首先，我们进行了体内实验，结果表明LNT可以抑制NB的肿瘤生长。随后的细胞功能分析显示，LNT处理可有效降低NB细胞活力，诱导细胞周期停滞在G0/G1期，增加凋亡率，削弱迁移和侵袭能力。此外，LNT导致FOS表达显著下调。FOS过表达可恢复被LNT抑制的NB细胞的生长、迁移和侵袭。机制研究表明，FOS与JUND相互作用，转录激活VRK1。此外，VRK1通过诱导p53 291-393位点的磷酸化来下调p53蛋白。总之，本研究揭示了LNT在NB中发挥肿瘤抑制功能的一种新的分子途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.