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首页> 外文期刊>Journal of experimental & clinical cancer research : >Overexpressed WDR3 induces the activation of Hippo pathway by interacting with GATA4 in pancreatic cancer
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Overexpressed WDR3 induces the activation of Hippo pathway by interacting with GATA4 in pancreatic cancer

机译：过表达的WDR3通过在胰腺癌中与GATA4相互作用诱导河马途径的激活

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WD repeat domain 3 (WDR3) is involved in a variety of cellular processes including gene regulation, cell cycle progression, signal transduction and apoptosis. However, the biological role of WDR3 in pancreatic cancer and the associated mechanism remains unclear. We seek to explore the immune-independent functions and relevant mechanism for WDR3 in pancreatic cancer. The GEPIA web tool was searched, and IHC assays were conducted to determine the mRNA and protein expression levels of WDR3 in pancreatic cancer patients. MTS, colony formation, and transwell assays were conducted to determine the biological role of WDR3 in human cancer. Western blot analysis, RT-qPCR, and immunohistochemistry were used to detect the expression of specific genes. An immunoprecipitation assay was used to explore protein-protein interactions. Our study proved that overexpressed WDR3 was correlated with poor survival in pancreatic cancer and that WDR3 silencing significantly inhibited the proliferation, invasion, and tumor growth of pancreatic cancer. Furthermore, WDR3 activated the Hippo signaling pathway by inducing yes association protein 1 (YAP1) expression, and the combination of WDR3 silencing and administration of the YAP1 inhibitor TED-347 had a synergistic inhibitory effect on the progression of pancreatic cancer. Finally, the upregulation of YAP1 expression induced by WDR3 was dependent on an interaction with GATA binding protein 4 (GATA4), the transcription factor of YAP1, which interaction induced the nuclear translocation of GATA4 in pancreatic cancer cells. We identified a novel mechanism by which WDR3 plays a critical role in promoting pancreatic cancer progression by activating the Hippo signaling pathway through the interaction with GATA4. Therefore, WDR3 is potentially a therapeutic target for pancreatic cancer treatment.
机译：WD重复域3（WDR3）涉及各种细胞过程，包括基因调控，细胞周期进展，信号转导和凋亡。然而，WDR3在胰腺癌中的生物学作用和相关机制仍不清楚。我们寻求探讨胰腺癌中WDR3的免疫独立功能和相关机制。搜索了Gepia Web工具，并进行了IHC测定以确定胰腺癌患者WDR3的mRNA和蛋白表达水平。进行MTS，菌落形成和Transwell测定以确定WDR3在人体癌症中的生物学作用。 Western印迹分析，RT-QPCR和免疫组织化学用于检测特定基因的表达。使用免疫沉淀测定探索蛋白质 - 蛋白质相互作用。我们的研究证明，过表达的WDR3与胰腺癌的存活率不良，并且WDR3沉默显着抑制胰腺癌的增殖，侵袭和肿瘤生长。此外，WDR3通过诱导是关联蛋白1（YAP1）表达而激活了Hippo信号传导途径，并且WDR3沉默和施用YAP1抑制剂TED-347的组合对胰腺癌的进展具有协同抑制作用。最后，WDR3诱导的YAP1表达的上调依赖于与GATA结合蛋白4（GATA4）的相互作用，YAP1的转录因子，其相互作用在胰腺癌细胞中诱导GATA4的核转移。我们确定了一种新的机制，通过通过与GATA4的相互作用激活河马信号通路来促进胰腺癌进展来发挥关键作用。因此，WDR3可能是胰腺癌治疗的治疗靶标。

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