Esophageal squamous cell carcinoma (ESCC) is a common malignancy with high morbidity and mortality. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) serves as a reader of RNA m6A (N6 methyladenosine) modification to regulate gene expression at the post-transcriptional level. Emerging evidence suggests that IGF2BP2 plays critical roles in tumorigenesis and malignant development. However, the biological function and molecular mechanism of IGF2BP2 in ESCC are not well understood. Here, we found that IGF2BP2 expression was upregulated in esophageal cancer tissues and ESCC cells, and IGF2BP2 overexpression enhanced proliferation, migration, invasion, and stem cell-like properties of ESCC cells. Conversely, the knockdown of IGF2BP2 expression inhibited malignant phenotype of ESCC cells. Mechanistically, IGF2BP2 upregulated octomer-binding transcription factor 4 (OCT4) mRNA expression, and RNA immunoprecipitation (RIP) assay proved that IGF2BP2 could interact with OCT4 mRNA. Moreover, OCT4 was modified at m6A confirmed by methylated m6A RNA immunoprecipitation (Me-RIP)-qPCR assay, and IGF2BP2 knockdown reduced OCT4 mRNA stability. These results suggested that IGF2BP2 served as a reader for m6A-modified OCT4, thus increased OCT4 mRNA expression by regulating its stability. Furthermore, the knockdown of OCT4 could reverse the effects of IGF2BP2 on ESCC cells. In conclusion, these data indicate that IGF2BP2, as a reader for m6A, plays an oncogenic role by regulating OCT4 expression in ESCC, which provides new insights into targeting IGF2BP2/OCT4 axis for the therapy of ESCC.

中文翻译：

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m6A阅读器IGF2BP2通过增加OCT4 mRNA的稳定性来促进食管鳞状细胞癌细胞的进展。

食管鳞状细胞癌（ESCC）是一种常见的恶性肿瘤，发病率和死亡率较高。胰岛素样生长因子 2 mRNA 结合蛋白 2 (IGF2BP2) 作为 RNA m6A（N6 甲基腺苷）修饰的读取器，在转录后水平调节基因表达。新的证据表明 IGF2BP2 在肿瘤发生和恶性发展中发挥着关键作用。然而，IGF2BP2在ESCC中的生物学功能和分子机制尚不清楚。在这里，我们发现IGF2BP2在食管癌组织和ESCC细胞中表达上调，并且IGF2BP2过表达增强了ESCC细胞的增殖、迁移、侵袭和干细胞样特性。相反，IGF2BP2表达的敲低抑制了ESCC细胞的恶性表型。从机制上讲，IGF2BP2上调八聚体结合转录因子4（OCT4）mRNA表达，RNA免疫沉淀（RIP）实验证明IGF2BP2可以与OCT4 mRNA相互作用。此外，通过甲基化 m6A RNA 免疫沉淀 (Me-RIP)-qPCR 测定证实 OCT4 在 m6A 处被修饰，并且 IGF2BP2 敲低降低了 OCT4 mRNA 的稳定性。这些结果表明IGF2BP2充当m6A修饰的OCT4的阅读器，从而通过调节其稳定性来增加OCT4 mRNA的表达。此外，敲低 OCT4 可以逆转 IGF2BP2 对 ESCC 细胞的影响。总之，这些数据表明IGF2BP2作为m6A的阅读器，通过调节ESCC中OCT4的表达发挥致癌作用，这为靶向IGF2BP2/OCT4轴治疗ESCC提供了新的见解。