Turk J Hematol. Ahead of Print: TJH-03592 | DOI: 10.4274/tjh.galenos.2025.03592

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

Wenyue Ma, Letian Sun, Siling Liu, Ning Hao
Nanjing University of Technology, School of Biological and Pharmaceutical Engineering, Nanjing, China

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 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.

Keywords: Acute myeloid leukemia, Neurexin 2, Insulin-like growth factor 2 mRNA binding protein 3, N6-methyladenosine

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