Objectives

Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms.

Methods

We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/β-catenin pathway.

Results

We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/β-catenin signaling, and that a Wnt/β-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells.

Conclusions

Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/β-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.

中文翻译：

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IFIT1通过Wnt/β-catenin信号传导调节胰腺癌细胞的增殖、迁移和侵袭

目标

此前，干扰素诱导蛋白四肽重复序列 1 (IFIT1) 已被证明可促进癌症发展。在这里，我们旨在探讨 IFIT1 在胰腺癌发生和进展中的作用，包括其潜在机制。

方法

我们使用癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 数据集探索了胰腺癌样本中的 IFIT1 表达。进行细胞计数试剂盒8（CCK8）、集落形成、划痕愈合和Transwell实验来评估胰腺癌细胞的增殖、迁移和侵袭能力。进行基因集富集分析 (GSEA) 和蛋白质印迹来评估 IFIT1 对 Wnt/β-catenin 通路的调节作用。

结果

我们发现 IFIT1 表达上调在胰腺癌中很常见，并且与患者的总体生存率呈负相关。 IFIT1表达的敲低导致胰腺癌细胞的增殖、迁移和侵袭减少。我们还发现 IFIT1 可以调节 Wnt/β-catenin 信号传导，而 Wnt/β-catenin 激动剂可以逆转这种效应。此外，我们发现IFIT1可以促进胰腺癌细胞的上皮间质转化（EMT）。

结论

我们的数据表明，IFIT1 通过激活 Wnt/β-catenin 通路来增加胰腺癌细胞的增殖、迁移和侵袭。此外，我们发现EMT可以受到IFIT1的调节。 IFIT1可能作为胰腺癌的潜在治疗靶点。