BACKGROUND The survival of pancreatic cancer patients remains poor. However, the underlying molecular mechanism and new therapeutic target of pancreatic cancer are still needed to be found. Many studies have shown that the IGF2 mRNA-binding protein 2 (IGF2BP2) plays oncogenic roles in cancers. However, the clinical significance, role and molecular mechanisms of IGF2BP2 in pancreatic cancer remain unclear. METHODS The expression of IGF2BP2 and miR-141 was detected in pancreatic cancer, and clinical significances were analyzed by statistical analysis. The function of IGF2BP2 and miR-141 was determined in vitro and in vivo, and the underlying mechanism was investigated. The gene copy number variation (CNV) of IGF2BP2 was analyzed based on The Cancer Genome Atlas (TCGA) dataset. microRNAs (miRNAs) regulating IGF2BP2 were predicted by online tools and confirmed by experiments. RESULTS IGF2BP2 is overexpressed in pancreatic cancer tissues compared with control tissues. Upregulation of IGF2BP2 predicts shorter overall survival (OS) in pancreatic cancer patients by statistical analysis. IGF2BP2 overexpression is partially due to genomic amplification. Bioinformatics analyses and validation experiments showed that IGF2BP2 is a direct target of miR-141. A negative correlation between IGF2BP2 mRNA expression and the expression of miR-141 was observed in pancreatic cancer tissues and more importantly, reexpression of miR-141 rescued the oncogenic role of IGF2BP2. Moreover, upregulating IGF2BP2 expression promotes pancreatic cancer cell growth by activating the PI3K/Akt signaling pathway in vitro and in vivo. CONCLUSIONS We comprehensively reveal the oncogenic role of IGF2BP2 in pancreatic cancer carcinogenesis and confirm that genomic amplification and the silencing of miR-141 contribute to its activation. Our findings highlight that IGF2BP2 may be a promising molecular target for the treatment of pancreatic cancer.

中文翻译：

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胰腺癌中通过多种机制上调IGF2BP2可以通过激活PI3K / Akt信号通路促进癌症的扩散。

背景技术胰腺癌患者的生存仍然很差。然而，仍需要寻找胰腺癌的潜在分子机制和新的治疗靶标。许多研究表明，IGF2 mRNA结合蛋白2（IGF2BP2）在癌症中起着致癌作用。然而，IGF2BP2在胰腺癌中的临床意义，作用和分子机制尚不清楚。方法检测胰腺癌中IGF2BP2和miR-141的表达，并通过统计学方法分析其临床意义。在体外和体内测定IGF2BP2和miR-141的功能，并研究其潜在机制。基于癌症基因组图谱（TCGA）数据集分析了IGF2BP2的基因拷贝数变异（CNV）。调控IGF2BP2的microRNA（miRNA）已通过在线工具进行了预测，并通过实验得到了证实。结果与对照组织相比，IGF2BP2在胰腺癌组织中过表达。通过统计分析，IGF2BP2的上调预测胰腺癌患者的总体生存期（OS）缩短。IGF2BP2过表达部分归因于基因组扩增。生物信息学分析和验证实验表明，IGF2BP2是miR-141的直接靶标。在胰腺癌组织中观察到IGF2BP2 mRNA表达与miR-141表达负相关，更重要的是，miR-141的重新表达挽救了IGF2BP2的致癌作用。此外，通过在体外和体内激活PI3K / Akt信号通路，上调IGF2BP2表达可促进胰腺癌细胞的生长。结论我们全面揭示了IGF2BP2在胰腺癌致癌作用中的致癌作用，并证实基因组扩增和miR-141沉默有助于其活化。我们的发现突出表明，IGF2BP2可能是治疗胰腺癌的有希望的分子靶标。