IGF2BP1 knockdown associates with alternative splicing changes of transcription factor genes in neuroblastoma cells
4 affiliations
- 1Department of Pediatrics, First Affiliated Hospital of Xi’an Jiaotong University
- 2Department of Pediatric Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University
- 3Department of Neonatology, Shaanxi Provincial People’s Hospital
- 4Department of Pathology, Xi’an Children’s Hospital
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.
Related
- G-Quadruplexes at the ‘Interface’ of Transcription and Alternative Splicing
- SRSF1 coordinates transcription and alternative splicing to modulate p53 and genome-maintenance
- Alternative splicing of a species- and skeletal muscle-specific microexon diversifies the menu of clathrin heavy chains in mice and rats
- Mitonuclear control of transcription complexes regulates tRNA splicing
- FET fusion proteins reshape splicing factor networks to drive oncogenic alternative splicing
BibTeX
@article{cheng2026igf2bp1,
title = {{IGF2BP1 knockdown associates with alternative splicing changes of transcription factor genes in neuroblastoma cells}},
author = {Jiwen Cheng and Pu Zhao and Junpeng Hui and Ping Cao},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1912388},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1912388/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - IGF2BP1 knockdown associates with alternative splicing changes of transcription factor genes in neuroblastoma cells
AU - Jiwen Cheng
AU - Pu Zhao
AU - Junpeng Hui
AU - Ping Cao
PY - 2026
DA - 2026/10/20
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1912388
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1912388/full
AB - 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.
SN - 2234-943X
ER -