Core transcriptional regulatory circuit-regulated IGF2BP3 stabilizes E2F2 mRNA via m6A modification in neuroblastoma

Year: 2025

Type: article

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.

Source: Carcinogenesis

DOI: 10.1093/carcin/bgaf040

Institutions: Soochow University, Northern Jiangsu People's Hospital, Children's Hospital of Suzhou University, Yangzhou University, China Pharmaceutical University

Language: English

Topic: RNA modifications and cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,835

Funders: Strong, Jiangsu Commission of Health, National Natural Science Foundation of China, Government of Jiangsu Province, Natural Science Foundation of Jiangsu Province, Soochow University, National Key Research and Development Program of China

OpenAlex ID: W4413309607