Turkish journal of haematology : official journal of Turkish Society of Haematology · 2025
IGF2BP3 Promoted the Overproliferation of AML Cells via Stability of NRXN2 mRNA.
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Ma Wenyue, Sun Letian, Liu Siling, Hao Ning
Аннотация
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 of AML were identified using the DESeq2 R package and verified by the TCGA-AML database. NRXN2 silencing, IGF2BP3 downregulation, and IGF2BP3 overexpression were performed in the human HL-60 AML cell line and proliferation and apoptosis were investigated. The potential m6A site of NRXN2 mRNA was predicted with the SRAMP website. IGF2BP3 enrichment and m6A modification of NRXN2 mRNA were detected by real-time polymerase chain reaction using the Magna MeRIP m6A Kit and by RNA immunoprecipitation real-time polymerase chain reaction, 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 overall survival. 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 the co-expression of the NRXN2 mutant.
CONCLUSION: IGF2BP3 promoted the stability of NRXN2 mRNA in an m6A-dependent manner, thereby promoting the overproliferation of AML cells.
MATERIALS AND METHODS: Differentially expressed genes of AML were identified using the DESeq2 R package and verified by the TCGA-AML database. NRXN2 silencing, IGF2BP3 downregulation, and IGF2BP3 overexpression were performed in the human HL-60 AML cell line and proliferation and apoptosis were investigated. The potential m6A site of NRXN2 mRNA was predicted with the SRAMP website. IGF2BP3 enrichment and m6A modification of NRXN2 mRNA were detected by real-time polymerase chain reaction using the Magna MeRIP m6A Kit and by RNA immunoprecipitation real-time polymerase chain reaction, 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 overall survival. 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 the co-expression of the NRXN2 mutant.
CONCLUSION: IGF2BP3 promoted the stability of NRXN2 mRNA in an m6A-dependent manner, thereby promoting the overproliferation of AML cells.