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

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

  • Cell Death Discov. 2025 Mar 15;11(1):103. doi: 10.1038/s41420-025-02315-0.
Zhang Zhao # 1,  Jiahao Li # 1,  Liyu Zhang # 1,  Jiayu Wang 1,  Dian Li 1,  Manna Zheng 1,  Zijie Ye 1,  Tianyou Yang 1,  Yan Zou 1,  Jing Pan 1,  Hui Xu 2,  Huijuan Zeng 3,  Chao Hu 4
Affiliations

Affiliations

  • 1 Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China.
  • 2 Department of Radiology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, Jiangsu, China. xunju933889@163.com.
  • 3 Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China. hjzeng_med@163.com.
  • 4 Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China. huchao032224@outlook.com.
  • # Contributed equally.
PMID: 40089488 DOI: 10.1038/s41420-025-02315-0
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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