m6A reader IGF2BP2 mediates paclitaxel resistance in esophageal squamous cell carcinoma via FOXM1 mRNA stabilization.

Esophageal squamous cell carcinoma (ESCC) ranks among the primary contributors to cancer‑related mortality in China. Resistance to paclitaxel markedly diminishes its therapeutic effectiveness and outcomes. Anaerobic glycolysis is a pivotal mechanism in cancer progression. Insulin‑like growth factor 2 mRNA binding protein 2 (IGF2BP2) as a reader of RNA N6‑methyladenosine (m6A) modification ensures the stability of RNA at the post‑transcriptional level. Nonetheless, the role and mechanism of IGF2BP2 in mediating paclitaxel resistance and anaerobic glycolysis in ESCC remain unclear. The current study selected two ESCC cell lines (KYSE30 and KYSE150). Cell proliferation and clonogenic ability were assessed via functional experiments. Apoptosis was quantified through flow cytometry. The rate of anaerobic glycolysis was determined via glycolysis assays. The stability of Forkhead box M1 (FOXM1) mRNA was assessed through reverse transcription‑quantitative polymerase chain reaction following actinomycin D treatment. Protein levels were analyzed through western blotting. Bioinformatics analysis revealed an overexpression of IGF2BP2 in ESCC. Furthermore, IGF2BP2 silencing inhibited cell proliferation and clonogenic activity. RNA and m6A‑sequencing results suggested that FOXM1 is critical to IGF2BP2‑mediated paclitaxel resistance in ESCC. Additionally, it was discovered that the silencing of IGF2BP2 compromises FOXM1 mRNA stability, reduces anaerobic glycolysis, and diminishes paclitaxel resistance. Finally, FOXM1 overexpression mitigated the effects of IGF2BP2 silencing in ESCC cells. The current findings underscore the significant role of the IGF2BP2‑FOXM1 signaling pathway in modulating anaerobic glycolysis and paclitaxel resistance in ESCC, offering insights into future therapeutic approaches to this malignancy.