Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, Henan Province, China.
Department of Information, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China.
World J Gastroenterol. 2019 Oct 28;25(40):6063-6076. doi: 10.3748/wjg.v25.i40.6063.
Studies have shown that insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) plays critical roles in the genesis and development of human cancers.
To investigate the clinical significance and role of IGF2BP1 in pancreatic cancer.
Expression levels of IGF2BP1 and microRNA-494 (miR-494) were mined based on Gene Expression Omnibus datasets and validated in both clinical samples and cell lines by quantitative real-time polymerase chain reaction and Western blot. The relationship between IGF2BP1 expression and clinicopathological factors of pancreatic cancer patients was analyzed. The effect and mechanism of IGF2BP1 on pancreatic cancer cell proliferation were investigated and . Analyses were performed to explore underlying mechanisms of IGF2BP1 upregulation in pancreatic cancer and assays were carried out to verify the post-transcriptional regulation of IGF2BP1 by miR-494.
We found that IGF2BP1 was upregulated and associated with a poor prognosis in pancreatic cancer patients. We showed that downregulation of IGF2BP1 inhibited pancreatic cancer cell growth and the AKT signaling pathway. Mechanistically, we showed that the frequent upregulation of IGF2BP1 was attributed to the downregulation of miR-494 expression in pancreatic cancer. Furthermore, we discovered that reexpression of miR-494 could partially abrogate the oncogenic role of IGF2BP1.
Our results revealed that upregulated IGF2BP1 promotes the proliferation of pancreatic cancer cells the AKT signaling pathway and confirmed that the activation of IGF2BP1 is partly due to the silencing of miR-494.
研究表明，胰岛素样生长因子 2 mRNA 结合蛋白 1（IGF2BP1）在人类癌症的发生和发展中发挥着关键作用。
研究 IGF2BP1 在胰腺癌中的临床意义和作用。
基于基因表达综合数据库（GEO）数据集挖掘 IGF2BP1 和 microRNA-494（miR-494）的表达水平，并通过实时定量聚合酶链反应（qRT-PCR）和 Western blot 在临床样本和细胞系中进行验证。分析 IGF2BP1 表达与胰腺癌患者临床病理因素的关系。研究 IGF2BP1 对胰腺癌细胞增殖的影响及其作用机制。分析探讨 IGF2BP1 在胰腺癌中上调的潜在机制，并进行实验验证 miR-494 对 IGF2BP1 的转录后调控作用。
我们发现 IGF2BP1 在胰腺癌患者中上调，并与预后不良相关。研究表明，下调 IGF2BP1 可抑制胰腺癌细胞生长和 AKT 信号通路。机制上，我们发现 IGF2BP1 的频繁上调归因于 miR-494 在胰腺癌中的表达下调。此外，我们发现 miR-494 的重新表达可以部分消除 IGF2BP1 的致癌作用。
我们的研究结果揭示了上调的 IGF2BP1 促进了胰腺癌细胞的增殖和 AKT 信号通路，证实了 IGF2BP1 的激活部分归因于 miR-494 的沉默。
