2. Academic Validation
  3. Core Transcriptional Regulatory Circuit-Regulated IGF2BP3 Stabilizes E2F2 mRNA via m6A Modification in Neuroblastoma

Core Transcriptional Regulatory Circuit-Regulated IGF2BP3 Stabilizes E2F2 mRNA via m6A Modification in Neuroblastoma

  • Carcinogenesis. 2025 Aug 18:bgaf040. doi: 10.1093/carcin/bgaf040.
Pengcheng Yang 1 2,  Jianwei Wang 1,  Ziheng Wu 1 3,  Ran Zhuo 1 4,  Yanling Chen 1,  Gen Li 1,  Yanfang Tao 1,  Xiaolu Li 1,  Fang Fang 1,  Di Wu 1,  Yang Yang 1,  Hongli Yin 1,  Guanghui Qian 1,  Hairong Wang 1,  Xin Li 3,  Juanjuan Yu 1,  Randong Yang 1,  Yunyun Xu 1,  Zhiheng Li 1,  Lei Shi 5,  Zimu Zhang 1,  Jian Pan 1,  Jian Wang 1 4
Affiliations

Affiliations

  • 1 Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou 215003, China.
  • 2 Department of Pediatric Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu 225000, China.
  • 3 Cardiothoracic Surgery Department, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, China.
  • 4 Department of Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, China.
  • 5 Department of Medicinal Chemistry, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University.
PMID: 40823720 DOI: 10.1093/carcin/bgaf040
Abstract

Neuroblastoma (NB) is a pediatric tumor with diverse outcomes and unknown underlying mechanisms. The core transcriptional regulatory circuit (CRC) and N6-methyladenosine (m6A) are key factors that control cell identity and fate. IGF2BP3 is an m6A reader protein that is transcriptionally regulated by CRC transcription factors (TFs). In NB, this molecule is abundantly expressed, and there is a clear correlation between its expression and a bad prognosis. We mechanistically demonstrated that IGF2BP3 promotes E2F2 mRNA expression through m6A, which is correlated with high risk and poor prognosis in NB patients. We showed that the CRC TF-IGF2BP3-E2F2 regulatory axis forms an oncogenic network that drives NB development and progression. Overall, we investigated the molecular mechanism by which IGF2BP3, a m6A-reading protein that is regulated by CRC TFs, regulates E2F2 mRNA expression in an m6A-dependent manner. This study highlights the therapeutic potential of disrupting this axis with m6A-targeted interventions.

Keywords

Core Transcriptional Regulatory Circuit (CRC); N6-methyladenosine (m6A); Neuroblastoma; m6A reader; mRNA stability.

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