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IGF2BP3 Promoted the Over-Proliferation of AML Cells via Stability NRXN2 mRNA

Year: 2025
Type: article
Abstract: Objective: Acute myeloid leukemia (AML) is a malignant tumor with high incidence and mortality.This study aimed to investigate whether insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) regulates the stability of neurexin 2 (NRXN2) mRNA in an N6-methyladenosine (m6A)-dependent manner and to explore its role in AML progression. Materials and Methods:Differentially expressed genes (DEGs) of AML were identified using DESeq2 R package, which was verified by TCGA-AML database.NRXN2 silence, IGF2BP3 downregulation and IGF2BP3 overexpression were performed in human AML cell line HL-60 cells, and proliferation and apoptosis were investigated.The potential m6A site of NRXN2 mRNA was predicted by SRAMP website.IGF2BP3 enrichment and m6A modification of NRXN2 mRNA were detected by MeRIP-qPCR and RIP-qPCR, respectively.An NRXN2 mutant lacking the predicted m⁶A site (NRXN2-mut (c.1770A>T)) was constructed and transfected into HL-60 cells Results: IGF2BP3 and NRXN2 were upregulated in AML, and their expression was negatively correlated with the overall survival of AML.A specific m⁶A modification site was identified on NRXN2 mRNA.NRXN2-mut (c.1770A>T) decreased the m⁶A modification level and reduced the stability of NRXN2 mRNA, as well as its enrichment by IGF2BP3.NRXN2 silencing and IGF2BP3 knockdown suppressed proliferation and promoted apoptosis in HL-60 cells, accompanied by decreased Bcl-2 and PCNA protein levels and increased cleaved caspase 3. IGF2BP3 overexpression promoted proliferation and inhibited apoptosis, effects that were reversed by co-expression of the NRXN2 mutant.Conclusion: IGF2BP3 promoted the stability of NRXN2 mRNA via m6A-dependent manner thereby promoting the over-proliferation of AML cells.
DOI: 10.4274/tjh.galenos.2025.03592
Language: English
Open Access status: diamond
OpenAlex ID: W4416416823
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