Core transcriptional regulatory circuit-regulated IGF2BP3 stabilizes E2F2 mRNA via m6A modification in neuroblastoma
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.
Authors
- Guanghui Qian (ORCID: https://orcid.org/0009-0005-5552-9125)
- Jian Wang (ORCID: https://orcid.org/0000-0001-9612-5382)
- Yunyun Xu (ORCID: https://orcid.org/0000-0002-6371-054X)
- Jian Pan (ORCID: https://orcid.org/0000-0002-0292-5141)
- Randong Yang
- Pengcheng Yang (ORCID: https://orcid.org/0000-0001-5496-8357)
- Jianwei Wang (ORCID: https://orcid.org/0000-0002-9765-3264)
- Gen Li (ORCID: https://orcid.org/0000-0003-0087-7796)
- Xiaolu Li (ORCID: https://orcid.org/0000-0002-3582-0792)
- Fang Fang (ORCID: https://orcid.org/0000-0002-1805-2031)
- Yang Yang (ORCID: https://orcid.org/0000-0001-6088-5435)
- Yanling Chen (ORCID: https://orcid.org/0000-0002-4511-0188)
- Di Wu (ORCID: https://orcid.org/0000-0001-5623-5819)
- Hairong Wang (ORCID: https://orcid.org/0009-0003-6835-0998)
- Ran Zhuo (ORCID: https://orcid.org/0000-0003-3180-643X)
- Lei Shi (ORCID: https://orcid.org/0000-0003-3583-4649)
- Hongli Yin (ORCID: https://orcid.org/0000-0002-5869-8072)
- Xin Li (ORCID: https://orcid.org/0000-0002-5976-2988)
- Yanfang Tao
- Juanjuan Yu
- Zimu Zhang (ORCID: https://orcid.org/0000-0003-0415-9425)
- Ziheng Wu
- Zhiheng Li (ORCID: https://orcid.org/0000-0002-2977-2624)
Institutions
- China Pharmaceutical University (CN)
- Soochow University (CN)
- Northern Jiangsu People's Hospital (CN)
- Children's Hospital of Suzhou University (CN)
- Yangzhou University (CN)
Publication Details
- Journal
- Carcinogenesis
- Published
- 2025-08-13
- DOI
- https://doi.org/10.1093/carcin/bgaf040
- Citations
- 1
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Strong
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province
- Soochow University