Work

IGF2BP1 knockdown associates with alternative splicing changes of transcription factor genes in neuroblastoma cells

Year: 2026

Type: article

Abstract: Background: IGF2BP1 is an oncofetal RNA-binding protein with oncogenic functions in neuroblastoma, but whether IGF2BP1 knockdown is associated with alternative splicing (AS) changes of transcription factor (TF) genes remains unclear. Methods: We re-analyzed RNA-seq data from IGF2BP1-knockdown BE(2)-C cells (three knockdown and three control samples). Differentially expressed genes (DEGs) and AS events (ASEs) were identified, followed by GO/KEGG enrichment. Differentially spliced genes were intersected with a human TF list. Isoform-specific qRT-PCR was performed in control and IGF2BP1-knockdown BE(2)-C cells to validate PSI changes. RIP-qPCR was used to test binding of IGF2BP1 to candidate TF mRNAs. ENCODE eCLIP-seq data from HepG2 and K562 cells were analyzed as indirect supportive evidence. Results: We identified 807 DEGs and 3, 053 significant ASEs. Among genes with significant splicing changes, 64 were annotated as TFs; 20 splicing events corresponding to 18 genes passed stringent filtering. Independent qRT-PCR validated the PSI changes of LMO4 (A5SS), TCF7L2 (cassette exon), and EHMT2 (exon skipping), which correlated with RNA-seq predictions. RIP-qPCR confirmed that IGF2BP1 binds to LMO4, TCF7L2, and EHMT2 mRNAs in cells, but not to NCOR2. eCLIP-seq data from non-neuroblastoma cell lines provided indirect supporting evidence. Conclusion: IGF2BP1 knockdown is associated with widespread AS changes of TF genes in neuroblastoma cells, and IGF2BP1 binds to LMO4, TCF7L2, and EHMT2 mRNAs. These findings provide a correlative resource and hypotheses for future mechanistic studies; direct causality remains to be established.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1912388

Authors: Jiwen Cheng, Pu Zhao, Junpeng Hui, Ping Cao

Institutions: First Affiliated Hospital of Xi'an Jiaotong University, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Shaanxi Provincial People's Hospital, Xi’an Children’s Hospital

Language: English

Topic: RNA Research and Splicing

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801