结肠直肠癌（CRC）是消化系统中最常见的恶性肿瘤之一，全球发病率和死亡率均排名第三。目前，尚无有效控制此类癌症的方法。在肿瘤细胞中，尤其是铁代谢对其生长和增殖至关重要。高水平的铁是维持肿瘤生长的重要特征，然而，整体机制仍不清楚。我们使用Western blotting、免疫组化（IHC）和实时定量PCR分析细胞系和组织中IGF2BP2的表达。进一步，RNA测序，RNA免疫共沉淀和甲基化RNA免疫共沉淀实验探讨了靶基因的特异性结合。此外，进行RNA稳定性试验以确定IGF2BP2下游基因的半衰期。此外，使用细胞计数试剂盒-8、集落形成实验、5-乙炔基-2'-脱氧尿嘧啶试验和流式细胞术评估IGF2BP2对增殖和铁代谢的影响。最后，在动物模型中证明了IGF2BP2促进CRC生长的作用。我们观察到IGF2BP2与铁稳态有关，TFRC是IGF2BP2的下游靶标。此外，TFRC的过表达可以挽救IGF2BP2敲除的CRC细胞的生长。机制上，我们确定IGF2BP2通过METTL4调节TFRC的甲基化，从而调节铁代谢并促进CRC生长。此外，在动物模型中观察到IGF2BP2促进CRC生长的作用。我们的研究突出了IGF2BP2在CRC癌变和铁运输途径中的关键作用。©2023年，作者（们）。

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, ranking third for morbidity and mortality worldwide. At present, no effective control method is available for this cancer type. In tumor cells, especially iron metabolization, is necessary for its growth and proliferation. High levels of iron are an important feature to maintain tumor growth; however, the overall mechanism remains unclear.We used western blotting, immunohistochemistry (IHC) and real-time quantitative PCR to analyze the expression of IGF2BP2 in cell lines and tissues. Further, RNA-sequencing, RNA immunoprecipitation and methylated RNA immunoprecipitation experiments explored the specific binding of target genes. Moreover, the RNA stability assay was performed to determine the half-life of genes downstream of IGF2BP2. In addition, the Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay and flow cytometry were used to evaluate the effects of IGF2BP2 on proliferation and iron metabolism. Lastly, the role of IGF2BP2 in promoting CRC growth was demonstrated in animal models.We observed that IGF2BP2 is associated with iron homeostasis and that TFRC is a downstream target of IGF2BP2. Further, overexpression of TFRC can rescue the growth of IGF2BP2-knockdown CRC cells. Mechanistically, we determined that IGF2BP2 regulates TFRC methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Furthermore, using animal models, we observed that IGF2BP2 promotes CRC growth.IGF2BP2 regulates TFRC mRNA methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Our study highlights the key roles of IGF2BP2 in CRC carcinogenesis and the iron transport pathways.© 2023. The Author(s).