TOB1 participates in various kinds of cancers. However, its role in pancreatic cancer has rarely been reported. In this study, we explored the expression and mechanisms of TOB1 in regulating the malignant phenotype of pancreatic cancer cells. TOB1 expression was determined by data mining and immunohistochemistry (IHC), and its localization was observed by immunofluorescence. CCK-8 cell proliferation, colony formation, flow cytometric, transwell migration, and Western blot (WB) assays were used to examine how it impacts the malignant phenotype of pancreatic cancer. Furthermore, Foxa2 binding to TOB1 was tested by dual-luciferase reporter assays, and RNA-Seq was performed to identify signaling pathways. We found TOB1 was downregulated in pancreatic cancer tissues and was mainly located in the cytoplasm. TOB1 overexpression reduced the proliferation of K-Ras wild-type pancreatic cancer cells but made no difference to cell migration and invasion. Foxa2 overexpression significantly enhanced TOB1 promoter activity. Moreover, overexpressing TOB1 substantially enriched the calcium pathway in K-Ras wild-type pancreatic cancer cells. In conclusion, TOB1 may suppress the proliferation of K-Ras wild-type pancreatic cancer cells by regulating calcium pathway genes.

中文翻译：

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TOB1抑制K-Ras野生型胰腺癌的增殖。

TOB1参与各种癌症。然而，其在胰腺癌中的作用鲜有报道。在这项研究中，我们探讨了TOB1在调节胰腺癌细胞恶性表型中的表达及其机制。通过数据挖掘和免疫组化（IHC）确定TOB1的表达，并通过免疫荧光观察其定位。使用CCK-8细胞增殖，集落形成，流式细胞术，transwell迁移和Western印迹（WB）分析来检查其如何影响胰腺癌的恶性表型。此外，通过双荧光素酶报告基因检测法测试了Foxa2与TOB1的结合，并进行了RNA-Seq识别信号通路。我们发现TOB1在胰腺癌组织中被下调，并且主要位于细胞质中。TOB1过表达减少了K-Ras野生型胰腺癌细胞的增殖，但对细胞迁移和侵袭没有影响。Foxa2过表达显着增强了TOB1启动子的活性。此外，过表达TOB1大大丰富了K-Ras野生型胰腺癌细胞中的钙途径。总之，TOB1可能通过调节钙途径基因来抑制K-Ras野生型胰腺癌细胞的增殖。