Taxol is widely used in the treatment of nasopharyngeal carcinoma (NPC); nevertheless, the acquired resistance of NPC to Taxol remains one of the major obstacles in clinical treatment. In this study, we aimed to investigate the role and mechanism of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in Taxol resistance of NPC. Taxol-resistant NPC cell lines were established by exposing to gradually increased concentration of Taxol. Relative mRNA and protein levels were tested using qRT-PCR and western blot, respectively. NPC cell viability and apoptosis were assessed by cell counting kit-8 and flow cytometry analysis, respectively. Cell migration and invasion capacities were measured using transwell assay. Interaction between IGF2BP1 and AKT2 was examined by RNA immunoprecipitation assay. The N6-methyladenosine level of AKT2 was tested using methylated RNA immunoprecipitation-qPCR. IGF2BP1 expression was enhanced in Taxol-resistant NPC cell lines. Knockdown of IGF2BP1 strikingly enhanced the sensitivity of NPC cells to Taxol and repressed the migration and invasion of NPC cells. Mechanistically, IGF2BP1 elevated the expression of AKT2 by increasing its mRNA stability. Furthermore, overexpression of AKT2 reversed the inhibitory roles of IGF2BP1 silence on Taxol resistance and metastasis. Our results indicated that IGF2BP1 knockdown enhanced the sensitivity of NPC cells to Taxol by decreasing the expression of AKT2, implying that IGF2BP1 might be promising candidate target for NPC treatment.

中文翻译：

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m6A reader IGF2BP1 通过上调 AKT2 降低鼻咽癌细胞对紫杉醇的敏感性。

紫杉醇广泛用于治疗鼻咽癌（NPC）；尽管如此，鼻咽癌对紫杉醇的获得性耐药仍然是临床治疗的主要障碍之一。本研究旨在探讨胰岛素样生长因子2 mRNA结合蛋白1（IGF2BP1）在鼻咽癌紫杉醇耐药中的作用及机制。通过暴露于浓度逐渐增加的紫杉醇来建立抗紫杉醇的NPC细胞系。分别使用 qRT-PCR 和蛋白质印迹测试相对 mRNA 和蛋白质水平。分别通过细胞计数试剂盒8和流式细胞术分析评估NPC细胞活力和凋亡。使用transwell实验测量细胞迁移和侵袭能力。通过 RNA 免疫沉淀测定检查 IGF2BP1 和 AKT2 之间的相互作用。使用甲基化 RNA 免疫沉淀 qPCR 测试 AKT2 的 N6-甲基腺苷水平。IGF2BP1 表达在紫杉醇抗性鼻咽癌细胞系中增强。IGF2BP1的敲低显着增强了NPC细胞对紫杉醇的敏感性并抑制了NPC细胞的迁移和侵袭。从机制上讲，IGF2BP1 通过增加 AKT2 mRNA 的稳定性来提高 AKT2 的表达。此外，AKT2 的过度表达逆转了 IGF2BP1 沉默对紫杉醇耐药和转移的抑制作用。我们的结果表明，IGF2BP1 敲低通过降低 AKT2 的表达来增强鼻咽癌细胞对紫杉醇的敏感性，这意味着 IGF2BP1 可能是鼻咽癌治疗的有希望的候选靶点。